Genetic technology for the synthesis and optimization of integrated reaction and separation systems uses rich superstructure formulations comprising two types of generic synthesis units with flexible representation modes. A reactor/mass exchanger unit enables a detailed representation of the reaction and mass exchange phenomena. A conceptual representation of separation systems is facilitated through separation task units. All possible process designs featuring reaction, reactive separation, and separation are embedded in the superstructure formulations as combinations of generic units and their features. The design options are explored using stochastic optimization techniques suitable for this class of problems. The flexible representation framework enables technology applications to general process design, as well as design subproblems including reactor and reactive separator design. Four case studies demonstrate the ability of the methodology to address a wide variety of process systems and to deliver design novelty.