The sustainability of the second-generation biofuels requests to confirm that the energy produced from lignocellulosic biomass is significantly greater than the energy consumed in the process. As lignocellulosic biomass does not affect the food supply, sugarcane bagasse was analyzed as a raw material for second-generation biofuels production. Exergy analysis serves as a unified and effective tool to evaluate the global process efficiency. Exergy analysis evaluates the performance of sugarcane bagasse and its sustainability in the bioethanol production process. In this work, four ethanol production topologies using the typical daily amount of residual biomass produced by the sugar industry were compared. The exergy analysis concept is effective in screening design alternatives with the lowest environmental impact for second-generation bioethanol fuel production from renewable resources. This study was executed by the use of the Aspen Plus® program and other software developed by the authors.