The reverse osmosis (RO) desalination process to make multiple freshwater from seawater has been studied in this work. The optimization method based on process synthesis has been applied to design the RO system. The optimum design problem can be formulated as a mixed-integer non-linear programming (MINLP) problem, which minimizes the total annualized cost of the RO system. The solution of the problem includes the optimal system structure and operating conditions, and the optimal streams distribution. The design method could also be used for the optimal selection of the types of membrane elements in each stages and the optimal number of membrane elements in each pressure vessel. The effectiveness of this design methodology has been demonstrated by solving a desalination case.