This study proposes a new operation methodology for energy saving in the Fujairah seawater reverse osmosis (SWRO) plant, as the optimum feed pressure is determined at the controlled operating temperature. To this end, two functional models were developed by genetic programming (GP) using two-year operational data. The data revealed that the required feed pressure for the plant operation was potentially overestimated. Based on the developed models, simulation of a three-step sequential control was carried out to reduce and optimize the required feed pressure. The simulation results first indicate that the temperature control significantly reduces the required feed pressure at a reasonably high temperature. Second, as the permeate water flow rate (PFR) is determined by the optimized feed pressure instead of the permeate pressure actually used to maintain a steady PFR in Fujairah, the required feed pressure could be substantially reduced. As a result, the proposed methodology can potentially reduce the required feed pressure, by approximately 10 bar, under the identical performance of both PFR and permeate water total dissolved solids (TDS). This study implies that the optimization of operation and management of MSF-hybridized SWRO processes can considerably improve the efficiency of the desalination process in terms of energy and, eventually, cost saving.