The global warming and climate change problems have become more serious because of the high consumption of fossil fuels during the past century. Recently, biofuels have attracted interest as an option to reduce the extensive use of fossil fuels; particularly, biobutanol appears as an option to replace the petroleum-based fuels. However, the separation process to produce biobutanol requires a lot of energy and yields lots of waste heat at low temperature. Therefore, there is a need to propose options to reduce the required energy in the biobutanol separation process. Consequently, this paper presents an optimization approach for designing energy integrated biobutanol separation processes. The optimization incorporates attractive separation options such as ABE fermentation using different solvents as well as incorporating several options for waste heat recovery involving integrated heat exchanger networks, stream Rankine cycles, organic Rankine cycles, and absorption refrigeration cycles. The results show significant economic and environmental benefits for the simultaneous consideration of the optimization of the separation process with the waste heat recovery for the biobutanol separation process.