Synthesis of heat exchanger networks including expansion process is a complex task due to the involvement of both heat and work. A stream that expands through expanders can produce work and cold load, while expansion through valves barely affects heat integration. In addition, expansion through expanders at higher temperature produces more work, but consumes more hot utility. Therefore, there is a need to weigh work production and heat consumption. To this end, an enhanced stage-wise superstructure is proposed that involves synchronous optimization of expander/valve placement and heat integration for each pressure-change sub-stream in stages. A mixed-integer nonlinear programming (MINLP) model is established for synthesizing sub and above-ambient heat exchanger networks with multi-stream expansion, which explicitly considers the optimized selection of end-heaters and end-coolers to adjust temperature requirement. Our proposed method can commendably achieve the optimal selection of expanders and valves in a bid for minimizing exergy consumption and total annual cost. Four example studies are conducted with two distinct objective function (minimization of exergy consumption and total annual cost, respectively) to illustrate the feasibility and efficacy of the proposed method. (C) 2020 The Chemical Industry and Engineering Society of China, and Chemical Industry Press Co., Ltd. All rights reserved.