The aim of this study is to analyze the exergetic, environmental, and economic impact of the electrification of a bio-refinery plant, considering the application of Mechanical Vapor Compression (MVC) to a conventional water–ethanol distillation column in the context of bioethanol production. The process was implemented in AspenPlus® and Aspen Exchange Design and Rating (EDR) simulation environments, where a sensitivity analysis was also carried out, considering four scenarios characterized by different compressions’ operative conditions, and including a Coefficient of Performance (CoP) analysis of the proposed solution with MVC. Exergetic and economic analyses were performed, and the relevant impacts on Operative Expenditure (OpEx) and Capital Expenditure (CapEx) were analyzed. Comparing the base case scenario with the proposed solution, a reduction of operative costs of around 63% was achieved. Finally, an environmental analysis was carried out, showing a remarkable reduction in the carbon footprint of the unit, with a carbon dioxide emission reduction of almost 80% for the MVC solution, in line with RED target requirements.