The ever-increasing world population, change in lifestyle, and limited natural water and energy resources have made industrial seawater desalination plants the leading contenders for cost-efficient freshwater production. In this study, the integration of a combined cycle power plant (CCPP) with multi-effect distillation (MED) and reverse osmosis (RO) desalination units is investigated through comprehensive conventional and advanced exergy, exergoeconomic, and exergoenvironmental analyses. Firstly, the thermodynamic modelling of the CCPP is performed by using a mathematical programming procedure. Then, a mathematical model is developed for the integration of the existing CCPP plant with MED and RO desalination units. Finally, conventional and advanced exergy, exergoeconomic, and exergoenvironmental analyses are carried out to assess the main performance parameters of the integrated CCPP and MED-RO desalination system, as well as to identify potential technical, economic, and environmental improvements. A case study is presented based on the Shahid Salimi Neka power plant located at the north of Iran along the Caspian Sea. The mathematical modelling approach for the integrated CCPP and MED-RO desalination system is solved in MATLAB, and the results are validated via Thermoflex software. The results reveal an increase of 3.79% in fuel consumption after the integration of the CCPP with the desalination units. The exergy efficiency of the integrated system is 42.7%, and the highest cost of exergy destruction of the combustion chamber is 1.09 US$ per second. Economic and environmental analyses of the integrated system also show that gas turbines present the highest investment cost of 0.047 US$ per second. At the same time, MED exhibits the highest environmental impact rate of 0.025 points per second.