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Seawater desalination is one of the most important means of securing water for domestic needs in arid geographical regions such as Saudi Arabia. Water production of Jeddah desalination plant is critical in meeting the city’s increasing water demands. The plant uses reverse osmosis technique with a production system consisting mainly of a permeate tank and production pumps. Failure or shutdown of any operating pump causes serious issues in demand and loss of production. The objective of this study is to develop a cost-effective operation policy that ensures the plant’s continuous production rate throughout the failure of any production pump. Mathematical optimization technique is used to explore possible and optimal solutions for the plant’s operation policies. The case was formulated as mixed-integer programming to minimize an objective function. POM-QM for Windows package was used to solve the problem using branch and bound method. This mathematical programming proved to be a powerful technique not only in solving for an optimal solution of a minimization problem, but also in generating a nearly optimal feasible solution of best operation policy in a given setting of water production system. The technique is capable of solving the optimal operation policy at minimal cost for any given scenario in the solution space under the shutdown condition of any operating pump. In addition to saving operational and maintenance costs, the obtained solutions can be adopted to prevent huge quantities of water production from being wasted into the sea. Hence, these solutions exhibit best practice and management of water resources.