There is rich literature on the separation of binary azeotropic mixtures, whereas few studies exist on the separation of biazeotropic ternary mixtures. In this work, we propose a systematic approach for energy-efficient extractive distillation processes for the separation of a biazeotropic mixture that involves thermodynamic insights via residue curve maps and the univolatility line to find the optimal entrainer and operating pressure, global optimization based on a proposed two-step optimization procedure, and double-effect heat integration to achieve further saving of energy consumption. An energy-saving reduced-pressure extractive distillation (RPED) with a heat integration flowsheet is then proposed to achieve the minimum total annual cost (TAC). The results show that the TAC, energy consumption, and exergy loss of the proposed RPED with heat integration are reduced by 75.2%, 80.5%, and 85.8% compared with literature designs.