Multiple-effect evaporation (MEE) is one of the energy-intensive processes. To reduce the energy consumption of this process, it is effective to integrate the MEE with its background process as a whole system. In this paper, a stage-wise superstructure model is proposed, which takes all possibilities in integration of the MEE coupled with its background process into consideration. The corresponding mathematical programming model, featuring a mixed-integer nonlinear programming formulation is then presented to minimize the total energy consumption (TEC) and the total annual cost (TAC) of the system. The optimal topology and operating parameters of the whole system are determined simultaneously by solving the proposed model. The application and effectiveness of the proposed model are illustrated through a case study of a concentrating sugar juice production process. The results obtained by the proposed method agree well with those obtained by the analytical methodology in literature when the energy demand is targeted. To further clarify the advantages of the proposed method, the coupled system with the lowest TAC is also analyzed and discussed, in which the stream matches and operating parameters are determined accordingly. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.