1. Theory of everything: Is there a singular, all-encompassing, coherent theoretical framework of physics that fully explains and links together all physical aspects of the universe?
2. Dimensionless physical constants: At the present time, the values of various dimensionless physical constants cannot be calculated; they can be determined only by physical measurement. What is the minimum number of dimensionless physical constants from which all other dimensionless physical constants can be derived? Are dimensional physical constants necessary at all?

1. Quantum gravity: Can quantum mechanics and general relativity be realized as a fully consistent theory (perhaps as a quantum field theory)? Is spacetime fundamentally continuous or discrete? Would a consistent theory involve a force mediated by a hypothetical graviton, or be a product of a discrete structure of spacetime itself (as in loop quantum gravity)? Are there deviations from the predictions of general relativity at very small or very large scales or in other extreme circumstances that flow from a quantum gravity mechanism?
2. Black holes, black hole information paradox, and black hole radiation: Do black holes produce thermal radiation, as expected on theoretical grounds? Does this radiation contain information about their inner structure, as suggested by gauge–gravity duality, or not, as implied by Hawking's original calculation? If not, and black holes can evaporate away, what happens to the information stored in them (since quantum mechanics does not provide for the destruction of information)? Or does the radiation stop at some point, leaving a black hole remnant? Is there another way to probe their internal structure somehow, if such a structure even exists?
3. The cosmic censorship hypothesis and the chronology protection conjecture: Can singularities not hidden behind an event horizon, known as "naked singularities", arise from realistic initial conditions, or is it possible to prove some version of the "cosmic censorship hypothesis" of Roger Penrose, which proposes that this is impossible? Similarly, will the closed timelike curves that arise in some solutions to the equations of general relativity (and that imply the possibility of backwards time travel) be ruled out by a theory of quantum gravity that unites general relativity with quantum mechanics, as suggested by the "chronology protection conjecture" of Stephen Hawking?
4. Holographic principle: Is it true that quantum gravity admits a lower-dimensional description that does not contain gravity? A well-understood example of holography is the AdS/CFT correspondence in string theory. Similarly, can quantum gravity in a de Sitter space be understood using dS/CFT correspondence? Can the AdS/CFT correspondence be vastly generalized to the gauge–gravity duality for arbitrary asymptotic spacetime backgrounds? Are there other theories of quantum gravity other than string theory that admit a holographic description?
5. Quantum spacetime or the emergence of spacetime: Is the nature of spacetime at the Planck scale very different from the continuous classical dynamical spacetime that exists in general relativity? In loop quantum gravity, the spacetime is postulated to be discrete from the beginning. In string theory, although originally spacetime was considered just like in general relativity (with the only difference being supersymmetry), recent research building upon the Ryu–Takayanagi conjecture has taught that spacetime in string theory is emergent by using quantum information theoretic concepts such as entanglement entropy in the AdS/CFT correspondence. However, how exactly the familiar classical spacetime emerges within string theory or the AdS/CFT correspondence is still not well understood.
6. Problem of time: In quantum mechanics, time is a classical background parameter, and the flow of time is universal and absolute. In general relativity, time is one component of four-dimensional spacetime, and the flow of time changes depending on the curvature of spacetime and the spacetime trajectory of the observer. How can these two concepts of time be reconciled?

1. Yang–Mills theory: Given an arbitrary compact gauge group, does a non-trivial quantum Yang–Mills theory with a finite mass gap exist? (This problem is also listed as one of the Millennium Prize Problems in mathematics.)
2. Quantum field theory (this is a generalization of the previous problem): Is it possible to construct, in a mathematically rigorous way, a quantum field theory in 4-dimensional spacetime that includes interactions and does not resort to perturbative methods?

1. Axis of evil: Some large features of the microwave sky at distances of over 13 billion light years appear to be aligned with both the motion and orientation of the solar system. Is this due to systematic errors in processing, contamination of results by local effects, an unexplained violation of the Copernican principle and thus the concordance model, or are these features simply statistically insignificant?
2. Fine-tuned universe: The values of the fundamental physical constants are in a narrow range that is necessary to support carbon-based life.[13][14][15] Is this because there are an infinite number of other universes with different constants, or are our universe's constants the result of chance, intelligent design (by a personal being such as the theist's "God"), or some other factor or process? (See also Anthropic principle.)
3. Cosmic inflation: Is the theory of cosmic inflation in the very early universe correct, and, if so, what are the details of this epoch? What is the hypothetical inflaton scalar field that gave rise to this cosmic inflation? If inflation happened at one point, is it self-sustaining through inflation of quantum-mechanical fluctuations, and thus ongoing in some extremely distant place?[16]
4. Horizon problem: Why is the distant universe so homogeneous when the Big Bang theory seems to predict larger measurable anisotropies of the night sky than those observed? Cosmological inflation is generally accepted as the solution, but are other possible explanations such as a variable speed of light more appropriate?[17]
5. Origin and future of the universe: How did the conditions for anything to exist arise? Is the universe heading towards a Big Freeze, a Big Rip, a Big Crunch, or a Big Bounce?
6. Size of universe: The diameter of the observable universe is about 93 billion light-years, but what is the size of the whole universe? Is the universe infinite?
7. Baryon asymmetry: Why is there far more matter than antimatter in the observable universe? (The apparent asymmetry in neutrino–antineutrino oscillations may suggest a solution.)[18]
8. Cosmological principle: Is the universe homogeneous and isotropic at large enough scales, as claimed by the cosmological principle and assumed by all models that use the Friedmann–Lemaître–Robertson–Walker metric, including the current version of the ΛCDM model, or is the universe inhomogeneous or anisotropic?[19] Is the CMB dipole purely kinematic, or does it signal anisotropy of the universe, resulting in the breakdown of the FLRW metric and the cosmological principle?[19] Is the Hubble tension evidence that the cosmological principle is false?[19] Even if the cosmological principle is correct, is the Friedmann–Lemaître–Robertson–Walker metric the right metric to use for our universe?[20][19] Are the observations usually interpreted as the accelerating expansion of the universe rightly interpreted, or are they instead evidence that the cosmological principle is false?[21][22]
9. Copernican principle: Are cosmological observations made from Earth representative of observations from the average position in the universe?
10. Cosmological constant problem: Why does the zero-point energy of the vacuum not cause a large cosmological constant? What leads to its cancellation?[23][24][a]

Estimated distribution of dark matter and dark energy in the universe

1. Dark matter: What is the identity of dark matter?[17] Is it a particle? If so, is it a WIMP, axion, the lightest superpartner (LSP), or some other particle? Or, do the phenomena attributed to dark matter point not to some form of matter but actually to an extension of gravity?
2. Dark energy: What is the cause of the observed accelerating expansion of the universe (the de Sitter phase)? Are the observations rightly interpreted as the accelerating expansion of the universe, or are they evidence that the cosmological principle is false?[21][22] Why is the energy density of the dark energy component of the same magnitude as the density of matter at present when the two evolve quite differently over time? Is this a cosmic coincidence? Is dark energy a pure cosmological constant or are models of quintessence such as phantom energy applicable?
3. Dark flow: Is a non-spherically symmetric gravitational pull from outside the observable universe responsible for some of the observed motion of large objects such as galactic clusters in the universe?
4. Shape of the universe: What is the 3-manifold of comoving space, i.e., of a comoving spatial section of the universe, informally called the "shape" of the universe? Neither the curvature nor the topology is presently known, though the curvature is known to be "close" to zero on observable scales. The cosmic inflation hypothesis suggests that the shape of the universe may be unmeasurable, but, since 2003, Jean-Pierre Luminet, et al., and other groups have suggested that the shape of the universe may be the Poincaré dodecahedral space. Is the shape unmeasurable; the Poincaré space; or another 3-manifold?
5. Extra dimensions: Does nature have more than four spacetime dimensions? If so, what is their size? Are dimensions a fundamental property of the universe or an emergent result of other physical laws? Can we experimentally observe evidence of higher spatial dimensions?

See also: Beyond the Standard Model

1. Hierarchy problem: Why is gravity such a weak force? It becomes strong for particles only at the Planck scale, around 1019 GeV, much above the electroweak scale (100 GeV, the energy scale dominating physics at low energies); why are these scales so different from each other? What prevents quantities at the electroweak scale, such as the Higgs boson mass, from getting quantum corrections on the order of the Planck scale? Is the solution supersymmetry, extra dimensions, or just anthropic fine-tuning?
2. Magnetic monopoles: Did particles that carry "magnetic charge" exist in some past, higher-energy epoch? If so, do any remain today? (Paul Dirac showed that the existence of some types of magnetic monopoles would explain charge quantization.)[25]
3. Neutron lifetime puzzle: While the neutron lifetime has been studied for decades, there is currently a lack of consilience on its exact value, due to different results from two experimental methods ("bottle" versus "beam").[26][b]
4. Proton decay and spin crisis: Is the proton fundamentally stable? Or does it decay with a finite lifetime as predicted by some extensions to the Standard Model?[27] How do the quarks and gluons carry the spin of protons?[28]
5. Grand Unification: Are the electromagnetic and nuclear forces different aspects of a Grand Unified Theory? If so, what symmetry governs this force and its behaviours?[29]
6. Supersymmetry: Is spacetime supersymmetry realized at TeV scale? If so, what is the mechanism of supersymmetry breaking? Does supersymmetry stabilize the electroweak scale, preventing high quantum corrections? Does the lightest supersymmetric particle (LSP) comprise dark matter?
7. Color confinement: The quantum chromodynamics (QCD) color confinement conjecture is that color-charged particles (such as quarks and gluons) cannot be separated from their parent hadron without producing new hadrons.[30] Is it possible to provide an analytic proof of color confinement in any non-abelian gauge theory?
8. 

Colour Confinement is the observed phenomenon that colored particles (quarks and gluons) cannot be isolated and are always bound to color neutral groups (at low energies). Such bound states are generally called hadrons.

1. The QCD vacuum: Many of the equations in non-perturbative QCD are currently unsolved. These energies are the energies sufficient for the formation and description of atomic nuclei. How thus does low energy/non-pertubative QCD give rise to the formation of complex nuclei and nuclear constituents?[citation needed]
2. Generations of matter: Why are there three generations of quarks and leptons? Is there a theory that can explain the masses of particular quarks and leptons in particular generations from first principles (a theory of Yukawa couplings)?[31]
3. Neutrino mass: What is the mass of neutrinos, whether they follow Dirac or Majorana statistics? Is the mass hierarchy normal or inverted? Is the CP violating phase equal to 0?[32][33]
4. Reactor antineutrino anomaly: There is an anomaly in the existing body of data regarding the antineutrino flux from nuclear reactors around the world. Measured values of this flux appears to be only 94% of the value expected from theory.[34] It is unknown whether this is due to unknown physics (such as sterile neutrinos), experimental error in the measurements, or errors in the theoretical flux calculations.[35]
5. Strong CP problem and axions: Why is the strong nuclear interaction invariant to parity and charge conjugation? Is Peccei–Quinn theory the solution to this problem? Could axions be the main component of dark matter?
6. Anomalous magnetic dipole moment: Why is the experimentally measured value of the muon's anomalous magnetic dipole moment ("muon g − 2") significantly different from the theoretically predicted value of that physical constant?[36]
7. Proton radius puzzle: What is the electric charge radius of the proton? How does it differ from a gluonic charge?
8. Pentaquarks and other exotic hadrons: What combinations of quarks are possible? Why were pentaquarks so difficult to discover?[37] Are they a tightly bound system of five elementary particles, or a more weakly bound pairing of a baryon and a meson?[38]
9. Mu problem: A problem in supersymmetric theories, concerned with understanding the reasons for parameter values of the theory.
10. Koide formula: An aspect of the problem of particle generations. The sum of the masses of the three charged leptons, divided by the square of the sum of the roots of these masses, to within one standard deviation of observations, is ⁠2/3⁠. It is unknown how such a simple value comes about, and why it is the exact arithmetic average of the possible extreme values of ⁠ 1 /3⁠ (equal masses) and 1 (one mass dominates).
11. Strange matter: Does strange matter exist? Is it stable? Can it form strange stars? Is strange matter stable at zero pressure (i.e. in vacuum)?
12. Glueballs: Do they exist in nature?
13. The gallium anomaly: The measurements of the charged-current capture rate of neutrinos on Ga from strong radioactive sources have yielded results below those expected, based on the known strength of the principal transition supplemented by theory.[39]

1. Solar cycle: How does the Sun generate its periodically reversing large-scale magnetic field? How do other solar-like stars generate their magnetic fields, and what are the similarities and differences between stellar activity cycles and that of the Sun?[40] What caused the Maunder Minimum and other grand minima, and how does the solar cycle recover from a minima state?
2. Coronal heating problem: Why is the Sun's corona (atmosphere layer) so much hotter than the Sun's surface? Why is the magnetic reconnection effect many orders of magnitude faster than predicted by standard models?
3. Astrophysical jet: Why do only certain accretion discs surrounding certain astronomical objects emit relativistic jets along their polar axes? Why are there quasi-periodic oscillations in many accretion discs?[41] Why does the period of these oscillations scale as the inverse of the mass of the central object?[42] Why are there sometimes overtones, and why do these appear at different frequency ratios in different objects?[43]
4. Diffuse interstellar bands: What is responsible for the numerous interstellar absorption lines detected in astronomical spectra? Are they molecular in origin, and if so which molecules are responsible for them? How do they form?[44][45]
5. Supermassive black holes: What is the origin of the M–σ relation between supermassive black hole mass and galaxy velocity dispersion?[46] How did the most distant quasars grow their supermassive black holes up to 1010 solar masses so early in the history of the universe?
6. Kuiper cliff: Why does the number of objects in the Solar System's Kuiper belt fall off rapidly and unexpectedly beyond a radius of 50 astronomical units?
7. Flyby anomaly: Why is the observed energy of satellites flying by planetary bodies sometimes different by a minute amount from the value predicted by theory?
8. Galaxy rotation problem: Is dark matter responsible for differences in observed and theoretical speed of stars revolving around the centre of galaxies, or is it something else?
   

   Rotation curve of a typical spiral galaxy: predicted (A) and observed (B). Can the discrepancy between the curves be attributed to dark matter?

9. Supernovae: What is the exact mechanism by which an implosion of a dying star becomes an explosion?
10. p-nuclei: What astrophysical process is responsible for the nucleogenesis of these rare isotopes?
11. Ultra-high-energy cosmic ray:[17] Why is it that some cosmic rays appear to possess energies that are impossibly high, given that there are no sufficiently energetic cosmic ray sources near the Earth? Why is it that (apparently) some cosmic rays emitted by distant sources have energies above the Greisen–Zatsepin–Kuzmin limit?[47][17]
12. Rotation rate of Saturn: Why does the magnetosphere of Saturn exhibit a (slowly changing) periodicity close to that at which the planet's clouds rotate? What is the true rotation rate of Saturn's deep interior?[48]
13. Origin of magnetar magnetic field: What is the origin of magnetar magnetic field?
14. Large-scale anisotropy: Is the universe at very large scales anisotropic, making the cosmological principle an invalid assumption? The number count and intensity dipole anisotropy in radio, NRAO VLA Sky Survey (NVSS) catalogue[49] is inconsistent with the local motion as derived from cosmic microwave background[50][51] and indicate an intrinsic dipole anisotropy. The same NVSS radio data also shows an intrinsic dipole in polarization density and degree of polarization[52] in the same direction as in number count and intensity. There are several other observations revealing large-scale anisotropy. The optical polarization from quasars shows polarization alignment over a very large scale of Gpc.[53][54][55] The cosmic-microwave-background data shows several features of anisotropy,[56][57][58][59] which are not consistent with the Big Bang model.
15. Age–metallicity relation in the Galactic disk: Is there a universal age–metallicity relation (AMR) in the Galactic disk (both "thin" and "thick" parts of the disk)? Although in the local (primarily thin) disk of the Milky Way there is no evidence of a strong AMR,[60] a sample of 229 nearby "thick" disk stars has been used to investigate the existence of an age–metallicity relation in the Galactic thick disk, and indicate that there is an age–metallicity relation present in the thick disk.[61][62] Stellar ages from asteroseismology confirm the lack of any strong age–metallicity relation in the Galactic disc.[63]
16. The lithium problem: Why is there a discrepancy between the amount of lithium-7 predicted to be produced in Big Bang nucleosynthesis and the amount observed in very old stars?[64]
17. Ultraluminous X-ray sources (ULXs): What powers X-ray sources that are not associated with active galactic nuclei but exceed the Eddington limit of a neutron star or stellar black hole? Are they due to intermediate-mass black holes? Some ULXs are periodic, suggesting non-isotropic emission from a neutron star. Does this apply to all ULXs? How could such a system form and remain stable?
18. Fast radio bursts (FRBs): What causes these transient radio pulses from distant galaxies, lasting only a few milliseconds each? Why do some FRBs repeat at unpredictable intervals, but most do not? Dozens of models have been proposed, but none have been widely accepted.[65]

1. Quantum chromodynamics: What are the phases of strongly interacting matter, and what roles do they play in the evolution of the cosmos? What is the detailed partonic structure of the nucleons? What does QCD predict for the properties of strongly interacting matter? What determines the key features of QCD, and what is their relation to the nature of gravity and spacetime? Does QCD truly lack CP violations?
2. Quark–gluon plasma: Where is the onset of deconfinement: (1) as a function of temperature and chemical potentials? (2) as a function of relativistic heavy-ion collision energy and system size? What is the mechanism of energy and baryon-number stopping leading to creation of quark-gluon plasma in relativistic heavy-ion collisions? Why is sudden hadronization and the statistical-hadronization model a near-to-perfect description of hadron production from quark–gluon plasma? Is quark flavor conserved in quark–gluon plasma? Are strangeness and charm in chemical equilibrium in quark–gluon plasma? Does strangeness in quark–gluon plasma flow at the same speed as up and down quark flavours? Why does deconfined matter show ideal flow?
3. Specific models of quark–gluon plasma formation: Do gluons saturate when their occupation number is large? Do gluons form a dense system called colour glass condensate? What are the signatures and evidences for the Balitsky–Fadin–Kuarev–Lipatov, Balitsky–Kovchegov, Catani–Ciafaloni–Fiorani–Marchesini evolution equations?
4. Nuclei and nuclear astrophysics: Why is there a lack of convergence in estimates of the mean lifetime of a free neutron based on two separate—and increasingly precise—experimental methods? What is the nature of the nuclear force that binds protons and neutrons into stable nuclei and rare isotopes? What is the explanation for the EMC effect? What is the nature of exotic excitations in nuclei at the frontiers of stability and their role in stellar processes? What is the nature of neutron stars and dense nuclear matter? What is the origin of the elements in the cosmos? What are the nuclear reactions that drive stars and stellar explosions? What is the heaviest possible chemical element?