Although a lot of effort has been directed toward individual utilization of CO2 and CH4, simultaneous transformation of CH4 and CO2 to acetic acid provides a green route for greenhouse gas utilization. However, the chemical inertness of both CH4 and CO2 hinders this process, and hence there is a need to design an effective catalyst that can easily facilitate this transformation. In this study, we have used a defective Fe2M (M = Mn, Fe, Co, Ni, Cu, Zn) metal–organic framework (MOF) node to computationally investigate the possibility of acetic acid synthesis from CH4 and CO2. Our study suggests that the presence of missing linker defects makes MIL-127 suitable for acetic acid synthesis, which otherwise was impossible in the pristine MOF. Again, heterometal substitution has an influence on the energetics of the reaction. Our study suggests that a heterometal, which simultaneously lowers the LUMO energy of the catalyst and increases the spin density on the hydrogen abstracting atom (H-AA), eases the process of C–H bond scission. A higher HOMO value of the intermediate formed after C–H bond dissociation has been found to enhance the CO2 insertion process. Detailed analysis predicts that Fe2Cu is an efficient catalyst for acetic acid synthesis. Since desorption of acetic acid is one of the important factors affecting the catalyst design, coadsorption of water molecules to Fe2Cu has been shown to enhance the acetic acid desorption process by a factor of about 14 with a desorption energy of 1.62 kcal/mol.