Rational design of high-efficient catalysts has been highly desired for renewable energy development. Density functional theory (DFT) calculations provides an efficient approach to explain the mechanisms of catalytic reactions via computing adsorption energies of reactants, especially, on metallic catalytic surface. However, it is still challenging to understand the underlying mechanisms in semiconductor-based catalysts because the prediction of the reaction rates is not using conventional linear descriptors obtained from DFT calculations. Moreover, since there are a lot of possible reaction intermediates in the methane oxidation process, it is time-consuming to investigate with a conventional trial-and-error approach. In this work, DFT calculations are employed to elucidate the preferred reaction pathway of methane oxidation depending on the Fermi level by combining with the Fermi-level dependent adsorption energy theory model for a semiconducting catalyst. Further, we investigated the underlying mechanisms of methane oxidation on CeO2 on metal-loaded/-doped CeO2 catalysts with various metal additives to enhance the catalytic activity.