Water desalination appears as an attractive alternative to provide fresh water in several parts of the world. However, this process is very expensive due to the high-energy consumption, and as consequence, significant pollution is produced due to the burning of fossil fuels that yield huge emissions of CO2. Furthermore, most of the desalination processes yield a lot of waste heat at low temperature, which can be recovered. Therefore, this paper presents an optimization approach for designing water desalination systems involving heat integration and waste heat recovery to reduce the desalination cost, energy consumption, and. overall greenhouse gas emissions. The proposed approach accounts for the optimal selection of existing and emerging desalination technologies based on the heating and cooling requirements and incorporating waste heat recovery systems. The integration of the proposed systems provides power and thermal energy to the desalination task. Also, the proposed approach includes the optimal selection of fossil fuels, biofuels, and solar energy as energy sources. The proposed approach was applied to a case study, and the results show that the system that involves the multiple-effect distillation and thermal membrane distillation shows the best economic and environmental benefits involving water sales, power production, and energy savings.