This paper presents a novel hybrid process combining thermally coupled reactive distillation with membrane-based pervaporation for enhanced production of n-butyl acetate. A conventional reactive distillation process was used as the base case and first optimized for the transesterification of methyl acetate with n-butanol to produce n-butyl acetate. It was observed that methyl acetate recovered in the recycle stream significantly affects the conversion in the reactive distillation column and overall energy efficiency of the whole process. The existing and proposed configurations were evaluated and optimized by simulation in Aspen Plus. The integration of thermally coupled reactive distillation and pervaporation improved the energy efficiency of the reactive distillation process by preventing remixing effect in the reactive distillation column and eliminating the azeotropic nature of the methanol and methyl acetate in the recycle stream, respectively. Finally, integration of the thermally coupled reactive distillation with a commercial pervaporation membrane was explored to take synergistic advantage of the thermally coupled reactive distillation and pervaporation hybrid configuration. As a result, the proposed hybrid design showed remarkably improved energy efficiency and economics. The total reboiler duty and total annual cost reduced to 63 and 43%, respectively, compared to those of the base case.