A techno-economic analysis for the separation process in bioethanol production is presented. Optimized azeotropic separation processes in conjunction with process integration (mass and energy) are considered to simultaneously enhance the results from economic and environmental points of view. Process integration improves significantly the separation process because it helps to reduce the overall energy required in the reboilers based on energy integration and additionally to diminish the amount of required solvent based on mass integration. The SYNHEAT optimization model was applied for energy integration whereas a direct recycle strategy was implemented for the mass integration process. The best separation processes obtained correspond to an integrated conventional separation sequence with energy integration to ethanol-water mixture III and integrated optional separation sequences with energy integration to ethanol-water mixture III, with significant savings in utility costs and possible recycling of nearly all solvent.