TWo significant forms of energy widely used in chemical industries are heat and work related to temperature and pressure manipulation. Since complex relationship exists in these strongly interacting properties (heat, work, temperature, pressure), it is essential to investigate work and heat integration as a whole. In this paper, an enhanced stage-wise superstructure is proposed that involves simultaneous optimization of compressor placement and heat integration for each pressure-changing sub-stream in stages. It explicitly considers non-isothermal mixing in each stage and enables the optimized selection of pre-coolers, end-heaters as well as end-coolers to adjust temperature requirements. A novel thermo-economic multi-objective mixed-integer nonlinear programming (MINLP) model is formulated to synthesize sub and above-ambient heat exchanger networks between constant-pressure streams and pressure-changing streams with multi-stream compression. The new model aims to achieve the optimal balance between thermodynamic and economic performances, with the objective of minimizing exergy consumption and total annual cost (TAC), respectively. Three case studies are conducted, where the results illustrate the well-known trade-off between thermodynamic and economic objective that is a decrease of 12.6%, 7.6%, 23.8% in TAC, while exergy consumption is increased by 14.8%, 12.8%, 4%. The Pareto curve is plotted for decision-makers to determine the optimal alternatives in terms of process requirement. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.