Metal-metal oxide (M-MO) interactions are important in catalysis. However, insights into how such interactions modulate lattice oxygen activity and stabilize critical reaction intermediates are scarce. In this work, using photocatalytic oxidative coupling of methane (POCM) as an example, we develop a simple and predictive model that defines M-MO interactions using two key factors: oxygen vacancy formation energy (EOV) and the methyl (*CH3) adsorption energy difference (ΔE*CH3) across metal and oxide sites. Interfacial coupling comodulates EOV and ΔE*CH3. EOV governs lattice-oxygen reactivity and the initial C-H activation, while ΔE*CH3 controls CH3 distribution between metal and oxide sites and thereby C-C coupling selectivity. Correlating EOV and ΔE*CH3 with activity and selectivity reveals a unifying principle. Efficient methane conversion requires moderately labile lattice oxygen whereas selective C-C bond formation demands a large ΔE*CH3 to drive methyl coupling for multicarbon products. Specifically, a AgPd/TiO2 catalyst achieves an optimal balance in experimental testing, delivering over a methane conversion yield of 30 mmol g-1 h-1, a selectivity of 92% for C2 products, and an operation stability of around 160 h. More broadly, the EOV-ΔE*CH3 framework provides a predictive descriptor map for M-MO photocatalysts selection in POCM. This study fills a critical gap by establishing a quantitative framework for M-MO interactions, identifying interfacial synergy as the principal determinant of performance, and enabling rational M-MO catalyst design.