Abstract This paper addresses the problem of how to synthesize mass and heat exchange processes, in which stream flowrates and their inlet compositions and temperatures may vary according to a set of discrete values. A unified hyperstructure representation of mass and heat exchange alternatives is introduced to account for all mass and heat integration possibilities. A multiperiod mixed integer nonlinear programming (MINLP) model is then developed, where a total annualized cost is minimized by balancing capital investment cost (of the heat and mass exchange equipment and their interconnections) to operating cost (of the hot-cold utilities, mass separating agents, etc.). As illustrated with the example problems, the proposed model can be effectively employed for the synthesis of flexible heat exchanger networks (HENs) and mass exchanger networks (MENs) separately or, for the synthesis of separation processes involving both heat and mass transfer.