Chemical process industries deal with production which further utilizes reaction followed by separation of the reaction mixtures. Reactive distillation is a new technique of combination of both reaction and separation in a single unit beneficial for equilibrium-limited reactions and also cost-effective. This makes it a highly complex process because many parameters involved in both reaction and separation are interactive in nature. In this chapter, modeling, simulation, and optimization of reactive distillation are presented. Methyl acetate production via reactive distillation is chosen as a case study. The results are compared for both experimental and simulation studies. The synthesis of methyl acetate was carried out in a packed RDC by catalytic esterification using acetic acid and methanol as reactants in a pilot-scale experimental setup. A strong acidic ion exchange catalyst, Amberlyst-15, was used to enhance the rate of heterogeneous esterification reaction. The result obtained was observed with change in various variables including the reflux ratio (RR), distillateto-feed (D/F) ratio, and bottom-to-feed (B/F) ratio with respect to product composition. The optimization and sensitivity analysis was carried out using Aspen Plus process simulation software.