A detailed exergy cost and thermoeconomic analysis applied to a Rankine Cycle (RC) coupled to a Multi-Effect Distillation (MED) plant was performed. The aim of this work is to identify the impact of design and operating conditions on the exergy and thermoeconomic costs of the final products, electricity, and freshwater, and to assess the distribution of the destroyed exergy, the fuel, and the plant costs. The plant model considers a high disaggregation model, which includes MED plant and condenser parasitic losses, a seawater pumping system and a brine energy recovery system. It also considers solar molten salts as the RC fuel, which is the typical fluid used in solar tower plants. The impact of RC + MED plant part-load operation, ambient temperature, MED plant size, and location plant’s altitude was evaluated and an analysis of operational day of the RC + MED plant was carried out. Results indicate that the plant part-load operation has a significant influence on the unit exergy and thermoeconomic product costs, while the ambient temperature evidences only a minor effect on the water costs. As well, the largest MED plant sizes (above 50,000 m3/day) offer the lowest electric and water costs, while the altitude strongly increases the water costs.