This study presents energy-efficient design alternatives for dimethyl carbonate production by combining various heat integration routes of reactive and pressure-sensitive distillation columns. The design of the hybrid heat-integrated sequences was based on internal and external heat integration with a vapor recompression heat pump (VRHP). The conventional pressure-swing separation design and the proposed hybrid heat integration processes were compared subject to a constraint of high product purity of 99.5%. The combined sequence of internal and external heat integration resulted in a cost reduction of 30.28% by eliminating the low-pressure (LP) column reboiler. The VRHP combined with external heat integration fully eliminated the heat duty of the high-pressure (HP) column condenser and the LP column reboiler, resulting in 38.33% energy savings and a 37.5% reduction in CO2 emissions. The two hybrid sequences with external heat integration showed better energy and economic efficiency and more reduced CO2 emissions than the VRHP combined with internal heat integration, since the reflux flow rate of the HP column and the reboil flow rate of the LP column were dramatically reduced.