Distillation with side-reactor (SRC) has already established its potential for understanding the energetic and economic performances of chemical processes. This study assesses the impact of operating pressure on reaction performances and overall economics in the SRC design. In conventional distillation operation, pressure is adjusted such that it permits the use of less expensive cooling water (318 K) in the condenser. However, the pressure of the nonreactive distillation column coupled to a side-reactor should be more carefully managed to obtain the process-intensification potential benefits. In the SRC design, the feed to the side-reactor is withdrawn from the column trays where the reactants are more abundant. Higher column pressure requires a more expensive heat source for the column base and causes temperature rise on the column trays. Depending on the kinetic parameters of the reaction, the pressure of the column can be adjusted to improve the conversion, selectivity, yield, and overall economics of the chemical process in an SRC design. A foremost trade-off between the operating pressure and reactor size/catalyst/heat load is demonstrated through three industrial-chemical processes. The outcome of this study affirmed the importance of understanding the impact, on process intensification, of selecting the appropriate operating pressure during the SRC conceptual design.