The unequal distribution of freshwater resources on Earth has spurred ongoing research to explore alternative sustainable desalination technologies to meet the demand for fresh water. This work features the development of a hierarchical control system incorporating a model predictive controller (MPC) and proportional-integral-derivative (PID) controllers for a fuel cell-integrated solar heated membrane desalination system, which was simulated using Simulink in MATLAB. The process disturbances were identified to be the solar irradiance and ambient temperature, while the manipulated variables were determined to be the seawater flow rate and H2 molar flow rate based on a sensitivity analysis. The hierarchical control system consisted of two levels, i.e., level 1 (base level) with the PID controllers and plant model, and level 2 with the MPC and feedback from the plant output. The system was revealed to be highly dependent on the MPC setpoint, with the optimal setpoint to maintain consistent total produced distillate (TPD) and profit to be around 5 kg h−1 and 6.5 × 10−5 USD s−1, respectively. The insights on the controller design and approach presented in this work are expected to benefit future membrane desalination system development.