In this paper, we propose a systematic procedure for the synthesis of feasible and optimal separation systems for nonideal mixtures by which entrainer and sequencing alternatives can be simultaneously explored. A multipurpose mass/heat exchange block is utilised as the building block to represent separation units and structures which are not explicitly pre-postulated but rather investigated as mass and heat exchange possibilities. Within this representation, feasibility of separation is ensured through systematic characterization of the mixture using detailed thermodynamic models and suitable mass driving force constraints. Once promising schemes have been identified, they can be considered further for detailed design optimization.