This paper is focused on modeling and optimization of spherical reactor configurations to produce dimethyl ether (DME) from methanol dehydration. A steady state heterogeneous one-dimensional mathematical model is developed based on the mass and energy conservation laws to predict the operability and performance of the proposed configurations. The spherical reactor is two concentric spheres that the space between spheres is filled by catalyst. To verify the accuracy of the considered model and assumptions, the simulation results of the conventional reactor are compared with the available plant data. The performance of the multi-stage spherical configurations is compared with the conventional industrial tubular reactor. In the optimization stage, DME production rate is maximized considering feasible decision variables using genetic algorithm as a powerful method in the global optimization. The simulation results show that increasing stages in the proposed spherical configuration enhances DME production capacity and decreases reactor diameter and thickness. (C) 2014 Elsevier B.V. All rights reserved.