Propylene/propane separation is one of the most energy-intensive processes in the chemical industry. In this study, the concepts of mechanical vapor recompression (MVR) and self-heat recuperation (SHR) are simultaneously considered for the synthesis of four distillation-based configurations. Each configuration is optimized for the minimum total annualized separation cost using a simulation-based optimization framework with Aspen HYSYS as the process simulator and particle swarm optimization in MATLAB as the optimizer. The best configuration uses both MVR and SHR. MVR eliminates the need for reboiler steam, and SHR utilizes the remaining sensible heat to preheat the feed and the compressor inlet stream in MVR. This reduces the energy consumption by 45% and the separation costs by 20% as compared to the values for an MVR design with no SHR.