Combined cycle power plants (CCPPs) use large amounts of water withdrawn from nearby rivers and generate wastewater containing ions and pollutants. Despite the need for wastewater reclamation, few technologies can successfully convert the wastewater into make-up water for CCPPs. Therefore, this study aimed to apply capacitive deionization (CDI) for wastewater reclamation in CCPPs. Using a bench-scale experimental unit, which included ion exchange membranes and carbon electrodes, response surface methodology (RSM) was used to optimize the operating conditions of the CDI process to increase the total dissolved solids (TDS) removal and product water ratio. The optimal conditions were found to be a voltage of 1.5 V, a flow rate of 15 mL/min, and an adsorption/desorption ratio of 1:0.8. The changes in CDI performance with time were also studied, and the foulants on the membranes, spacers, and electrodes were examined to understand the fouling mechanism. The TDS removal decreased from 93.65% to 55.70% after 10 days of operation due to the deposition of scale and organic matter. After chemical cleaning, the TDS removal rate recovered to 93.02%, which is close to the initial condition.