In this work a mathematical programming methodology is proposed for the efficient optimization of hybrid separation systems consisting of distillation columns and membrane separation units. A superstructure representation of the alternative solutions is first presented. This superstructure is obtained by modifying an existing superstructure for distillation columns and combining with a recently proposed superstructure for gas permeation networks. The final morphological representation is then used for the structural and parametric optimization of a hybrid system for the propylene/propane separation (C-3 splitter). The results are noticeably different from the results of previous case studies on the same separation and show that the economic potential for using hybrid systems can be significant.