In this work, we propose a methodology to solve a nonlinear mathematical model for the optimal design of reverse osmosis (RO) networks, which ameliorates the shortcomings of the computational performance and sometimes convergence failures of commercial software to solve the rigorous mixed integer nonlinear programming (MINLP) models. Our strategy consists of the use of a genetic algorithm to obtain initial values for a full nonlinear MINLP model. In addition, because the genetic algorithm based on the rigorous model equations is insurmountably slow, we use metamodels to reduce the mathematical complexity and considerably speed up the run. We explore the effects of the feed flow, seawater concentration, number of reverse osmosis stages, and the maximum number of membrane modules in each pressure vessel on the total annualized cost of the plant.