Ce-based oxides doped with different metal ions can greatly improve CH4 catalytic activity, but the relationship between the surface microstructure and its activity is not clear. In this article, M(Y, Sm, and Ni)-CeO2 catalyst prepared by aerosol method is used as the research object. CH4 is used as a molecular probe for the study. Operando DRIFTS-MS and DFT computation are used to verify the structure-activity relationship between the surface structure and activity of M-CeO2. Ni-CeO2 with the smallest atomic radius ratio has the best CH4 oxidation performance (550 °C) and excellent redox characteristics. Operando DRIFTS-MS results show that the NiO is more likely to adsorb CH4 and form the intermediates CH3*, gas-phase CO2, CO, and H2O at low temperatures. At high temperatures, Ni-OH, Ni-O-Ce, and CeO further react with CH4. Among them, the formation of M-Ov-Ce has a positive role in promoting the decomposition of O₂. Importantly, carbonate is the rate-determining step that affects the activation of M-Ov-Ce. Monodentate carbonates decompose more easily at low temperatures. These findings reveal a novel doping effect and provide a new idea for the design and development of Ce based catalysts with high CH4 removal ability