A typical 1000 MW Pressurized Water Reactor (PWR) nuclear power plant coupled to a multi effect distillation desalination system with a thermo-vapor compressor (MED-WC) is considered for optimization. The thermodynamic modeling is performed based on the energy and exergy analyses, while an economic model is developed according to the Total Revenue Requirement (TRR) method. The objective functions based on the thermodynamic and thermoeconomic analyses are obtained. The proposed hybrid plant with ten decision variables for power plant and six decision variables for the desalination plant is optimized in a multi-objective optimization process. This approach is applied to minimize either the cost of the system product (including the cost of generated electricity and fresh water) and/or maximize the exergetic efficiency of the system. Three optimization scenarios including thermodynamic single objective, thermoeconomic single objective and multi-objective optimizations are performed using the Genetic Algorithm (GA). In multi-objective optimization, both thermodynamics and thermoeconomic objectives are considered, simultaneously. A series of optimum solutions namely Pareto frontier is obtained. In the case of multi-objective optimization, an example of decision-making process for selection of the final optimal solution from the available optimal points on the Pareto frontier is introduced. The results obtained using the various optimization scenarios are compared and discussed. (C) 2010 Elsevier B.V. All rights reserved.