A large-scale dimethyl carbonate (DMC) production process from ethylene oxide (EO), CO2, and methanol was simulated and optimized. Unlike most industrial processes of DMC production, the direct conversion of EO and CO2 to ethylene carbonate (EC) and EC transesterification to DMC were performed in a single reactor. The reaction volume and the reactor operating pressure were selected as decision variables and evaluated. The key performance parameters, e.g., conversion per pass and CO2 intensity, were compared with conventional commercialized routes or novel promising processes in the literature.