van der Waals density functional theory (vdW-DFT) and semiempirical grand canonical Monte Carlo (GCMC) calculations are used to predict the thermodynamics and methane storage capacity of 18 metal-substituted variants of the metal–organic framework (MOF) M-DOBDC (DOBDC = 2,5-oxidobenzene-1,4-dicarboxylate). Methane adsorption enthalpies (ΔH) on the benchmark Mg- and Ni-DOBDC systems were calculated using several vdW-DFT methods. The vdW-DF2 scheme was found to yield the best agreement with experiments, with a mean absolute deviation (MAD) of 2.7 kJ/mol. Applying this functional across the entire M-DOBDC series, it is observed that ΔH varies from −16 to −34 kJ/mol. These enthalpies are 10–20 kJ/mol less exothermic than that for CO2 adsorption in M-DOBDC, consistent with a weaker, dispersion-based CH4–MOF interaction. In parallel with these thermodynamic analyses, methane adsorption isotherms for five benchmark M–DOBDC MOFs were evaluated using several established interatomic potentials. An uncharged, single...