Solar-driven membrane distillation (SDMD) for desalination is a feasible method to solve water and energy resource issues. The design and operation of SDMD is different from continuous and steady state processes, such as common chemical plants, due to the intermittent and unpredictive characteristics of solar radiation. Employing the steady state and dynamic simulation models developed on the platform of Aspen Custom Modeler®, this paper presents a two-stage design approach for the SDMD systems using different types of membrane distillation configurations, including AGMD (air gap MD), DCMD (direct contract MD) and VMD (vacuum MD). The first design stage uses the steady state simulation model and determines equipment sizes for different constant-value solar radiation intensities with the objective of minimizing total annual cost. The second design stage is implemented on the SDMD systems with process control to automatically adjust the operating flow rates using the dynamic simulation model. Operated with the yearly solar radiation intensity of Taiwan, the unit production costs (UPCs) of the optimal SDMD systems using AGMD, DCMD, and VMD are $2.71, 5.38, and 10.41 per m3 of water produced, respectively. When the membrane unit cost is decreased from $90/m2 to $36/m2, the UPC of the optimal solar-driven AGMD system can be reduced from $2.71/m3 to $2.04/m3.