AbstractWater supply challenges are caused by population growth, industrialization, as well as the scarcity of freshwater resources. Low‐grade waste heat‐driven seawater desalination technologies may improve the water‐energy nexus issues of desalination systems by different configurations. The data envelopment analysis is used to determine the best final decision to achieve a better comparison of different parameters. The optimal configuration of low‐grade waste heat driven seawater desalination is studied using flue gas waste heat in heat recovery boilers of an industrial oil refinery. Nine different types of multistage flash and multi‐effect distillation (MED) desalination plants have been considered. The results show that the multistage flash brine recirculation may produce more desalinated water while the multi‐effect distillation with three stages (3‐stage MED) has the best payback period. Using 3‐stage MED with a production of approximately 19,630 kg/h of water from 5.3 MW exhaust gas is more suitable for this design. Thus, the proposed strategy guides us toward the best decisions to configure low‐grade waste heat‐driven desalination plants for better design considering rigorous simulations for the plants. Moreover, this framework enables us to consider different criteria of technical, economic, and environmental issues for optimal configuration.