Reactive distillation is a highly efficient process, but its application presents significant challenges in mixtures that have azeotropes, such as in the transesterification of methyl acetate (MeAc) and methanol (MeOH) with n-butanol (BuOH). This paper proposes a reactive distillation with a prefractionation column (RDPFC) system to valorize the waste stream from the poly-(vinyl alcohol) industry (30.7 wt % MeAc and 69.3 wt % MeOH) to recover high-purity MeOH and valuable n-butyl acetate (BuAc). The process was modeled and optimized in Aspen Plus version 12.1, with the objective of minimizing the total annual cost (TAC). The proposed system incorporates a prefractionation column (PFC) consisting of 26 stages working under vacuum conditions (0.6 atm) alongside a reactive column (RC) with 38 stages operating at high pressures (8 atm) to improve the conversion of the reaction. The RDPFC process attains a MeAc conversion rate of 99.2 mol %, yielding products that align with commercial specifications, including over 99.85 wt % MeOH and more than 99.5 wt % BuAc. A comparative analysis reveals that the RDPFC configuration utilizes 2.56 GJ/tBuAc, showcasing a significant 67% reduction in energy consumption when compared to the traditional reactive and extractive distillation (RED) process. The removal of the entrainer and its corresponding recovery unit primarily accounts for this improvement. This study suggests that the RDPFC system could be a highly efficient and economically attractive solution for valuing waste streams in the poly-(vinyl alcohol) industry.