To achieve net-zero CO2 emissions by 2050, improving energy efficiency in the chemical industry is crucial. The study focuses on an environmentally friendly hybrid distillation (D)-pervaporation (PV) process to enhance energy efficiency and purity in ethanol–water and isobutanol-water mixtures, these are typical wastes in the chemical industry. Three configurations—D + PV, D + PV + D, and D + PV + D with partial Heat Integration (HI)—are evaluated for separation of ethanol–water and isobutanol-water mixtures employing the Life Cycle Assessment with Environmental Footprint (EF) V3.1 (adapted) and ReCiPe 2016 Endpoint (H) V1.08 methods, using SimaPro V9.5 software and Ecoinvent V3.9.1 database. The study also incorporates a PESTLE analysis and Multi-Criteria Decision Analysis to identify the most advantageous process for ethanol and isobutanol scenarios. The research evaluates these systems in a comprehensive manner, including technology, CO2 emissions, impacts on human health, ecosystems, resources, and Total Annual Cost (TAC). The exploration of hybrid process enhancements includes alternative renewable energy sources (i.e., solar, wind, hydro, and biofuel) and comprehensive heat integration based on Pinch Analysis using Hint V2.2 software. Results indicate that D + PV + D is the most suitable for isobutanol-water scenarios based on MCDA and Pinch analysis. In isobutanol scenarios, D + PV + D + HI reduces CO2 emissions, and human health, ecosystems, and resources impact by 15.5 %, 11.2 %, 12.6 %, and 14.6 %, respectively, with a significant 40.0 % decrease in TAC compared to D + PV. Integrating renewable energy sources further enhances its sustainability, achieving a single score of approximately one-third lower than fossil fuel consumption. Promoting renewable energy and Integrating energy flows align seamlessly with Green Chemistry and Engineering principles, representing a crucial stride towards sustainable and eco-friendly industrial practices.