This study reports the advantages of a cost-effective unit process using a hybrid distillation and vapor permeation unit for isopropanol dehydration. The feasibility of numerous hybrid membrane distillation schemes for isopropanol dehydration was evaluated by simulation and optimization in Aspen Plus. A built-in model for a membrane separation system was proposed by developing a mathematical model in an Aspen Custom Modeler and integrating it simultaneously with an Aspen Plus. The output results of the rigorous membrane models were consistent with the experimental data from the literature. The influence of the decisive operational parameters, which will be used as an optimization variable to examine the different configurations of hybrid systems, was analyzed. Furthermore, this study also employed the response surface methodology (RSM) to optimize the economical calculation and find the best design for the desired product. The RSM optimization effectively connected the interception of the optimizing variables and its predictions agreed well with the results of rigorous simulations. The most significant savings in the total costs could be achieved by applying a distillation-vapor permeation configuration (approximately 77% compared to azeotropic distillation). Therefore, it is economically beneficial to employ distillation-vapor permeation over the previously proposed hybrid systems of the distillation-pervaporation and distillation-pervaporation-distillation. (C) 2015 Elsevier B.V. All rights reserved.