The mathematical model developed in this paper deals with simultaneous synthesis of the integrated separation network, where both mass separating agents (MSAs) and energy separating agents (ESAs) are taken into account. The proposed model formulation is believed to be superior to the available ones. Traditionally, the tasks of optimizing ESA-based and MSA-based processes were either performed individually or studied on a heuristic basis. In this work, both kinds of processes are incorporated into a single comprehensive flowsheet and a novel state-space superstructure with multi-stream mixings is adopted to capture all possible network configurations. By properly addressing the issue of interactions between the MSA and ESA subsystems, lower total annualized cost (TAC) can be obtained by solving the corresponding mixed-integer nonlinear programming (MINLP) model. A benchmark problem already published in the literature has been investigated to demonstrate how better conceptual designs can be generated by our proposed approach. (C) 2010 Elsevier Ltd. All rights reserved.