<p>Simultaneous growth in energy and freshwater consumption has led to the need for advanced waste heat recovery systems in fossil-fuel power plants. This paper presents energy, exergy, exergoeconomic, and environmental (4E) performance of a modified polygeneration system applied to such plants. The novelty of this study lies in the comprehensive 4E assessment and optimization of a uniquely integrated intercooled-reheated gas-steam cycle with humidification-dehumidification (HDH) desalination, demonstrating how this specific configuration simultaneously maximizes power and freshwater generation while minimizing economic and environmental costs. This involves a near-atmospheric condenser pressure of 105&#xa0;kPa to allow production of a combined power and freshwater generation system by providing the HDH processes with the thermal energy required for this. The strategies also involve coupling the minimum capital cost with the ideal performance by a mass flow ratio (MR) of 2. On the level of components, the intercooler has the largest exergy destruction of 34.74% due to low level rejection of heat. The plant’s exergy efficiency was estimated to be reasonable at 51.4% with an optimized design. Sensitivity analysis indicates the feasibility of the integrated plant design at a fuel cost of 0.0065 $/MJ. These results show a cascading waste heat recovery system’s ability to considerably reduce both the levelized cost of products (LCOP) and environmental impact compared to stand-alone heat recovery systems.</p>