In this research, an exergetic mathematical model is proposed for closed-loop food supply chain network design considering economic, environmental, and social aspects. The studded closed-loop food supply chain consists of six echelons, four echelons for forwarding the products (suppliers, factory, distribution centers, and customers), and two echelons for returning the products (collecting centers and disposal centers). The exergetic model is based on the extended exergy accounting method, which calculates the consumed exergy in all six echelons by considering the equivalents of labor and capital exergy. This model aims to minimize both the economic and exergetic costs associated with the food supply chain. To solve the proposed mathematical model, an ensemble global–local search metaheuristic algorithm utilizing a combined whale optimization algorithm (WOA) and simulated annealing (SA), called CWOASA, is proposed. In the CWOASA algorithm, first, WOA is used to search the entire search space. Next, SA is applied to further improve the best solution obtained by WOA. A real dataset of a dairy supply chain is used to evaluate the efficiency of the proposed metaheuristic-driven exergy analysis model and claim its benefits over the existing methods. Simulation results revealed that the proposed method leads to a 6.74% reduction in the total exergy consumption of the supply chain. The proposed methodology offers valuable insights, shedding light on the prospective gains in terms of mitigated environmental impact for each incremental economic expenditure, thus laying the foundation for promising avenues of future research.