Finally, we summarize these design principles to identify strategies for enhancing the selectivity of MOFs for either CO2 or CH4 gas adsorption. For high-throughput screening, our RF models revealed that computed void volume and surface area of MOFs should serve as predictive indicators of gas adsorption preferences. Additionally, since trinuclear metal clusters [M3O(O2C-)6] (i.e., N38 and N61) show a preference for CO2 over CH4, substituting these metal clusters with different metal atoms also in a +3 oxidation state (e.g., V, Cr, Mn, and Co) could be a strategy to tailor MOFs for high selectivity for CO2 while introducing metal diversity. To construct MOFs exhibiting a preference for high CH4 working capacity over CO2, employing longer edges and connectivity nets characterized by large void volumes and small surface areas should serve as the most effective design strategies. As a secondary strategy, node identities are also informative: open metal sites are likely to enhance CO2 adsorption. Conversely, robust nodes contribute to mechanically stable structures even when combined with long edges in order to create large void volumes that contribute to CH4 adsorption enhancement. These principles cannot be observed in CoRE MOF 2019 due to the absence of MOFs with higher CH4 working capacities in previously synthesized MOFs. However, we anticipate these design principles should aid in the future identification of candidate MOFs as synthetic targets or for assessment of synthesized MOFs that have not been deposited in structural databases.