Using a high-throughput virtual screening (HTVS) approach, we investigated 2,048 codoped transition metal (i.e., Mn, Fe, Co, and Ru) SACs in numerous spin and oxidation states for the challenging conversion of methane to methanol. Here, we focused on modulating the coordination environment by doping in both the first and second coordination spheres, to design efficient SACs and alter the catalytic properties for direct methane-to-methanol conversion. To determine the ground spin state of catalytic intermediates of SACs, we first explored the impact of the influence of metal/oxidation state in SACs. We found that SACs can have either IS or LS ground states in the catalytic cycle depending on the transition metal center. Next, we evaluated the relationship of the energetics of oxo formation and HAT steps in codoped transition metal SACs. Across our codoped SACs dataset, we observed a relatively weak negative correlation between ΔE(oxo) and ΔE(HAT). We attribute the weak correlation to the significant variation of the coordination environment among these SAC catalysts, especially the structural variation in the first coordination sphere. The ΔE(release) energetics are endothermic for the codoped SACs, with a wide-spread range for Fe and Mn codoped SACs but are quite narrow for Co and Ru codoped SACs. We expect the flexible tunability demonstrated here, which allows disruption of LFERs as in molecular catalysts, should combine with the stability and scalability of SAC catalysts in general to benefit from the advantages of both homogeneous and heterogeneous catalysts. In order to understand the periodic trends and coordination environment effects on reaction energetics, we compared Fe and Ru reaction energetics and found Ru formed more stable metal-oxos, while Fe HAT energetics were more favorable. Conversely, ΔE(HAT) energetics in LS Ru codoped SACs are less favorable than those in all LS Fe SACs, and most IS Ru systems exhibit far less favorability than IS Fe systems.