A simulation-optimization approach is a suitable tool in waste load allocation problems when considering competing objectives and complex pollutant fate and transport processes in water bodies. Here, an archived multi-objective simulated annealing (AMOSA) algorithm is developed to determine various decision variables related to multi-pollutant waste load allocation (MPWLA) problems. The developed AMOSA algorithm has been coupled to QUAL2Kw in order to derive optimal MPWLA programs in Gheshlagh River, Kordestan, Iran. Minimizing wastewater treatment plant (WWTP) costs, improving the EquityMeasure, and enhancing water quality index (WQI) of the river have been considered as objective functions of MPWLA problems. The applied WQI integrates various water quality parameters (biochemical oxygen demand (BOD), dissolved oxygen (DO), NH4-N, NO3-N, PO4-P, total suspended solids (TSS), and Coliform) in monitoring stations along the river. Results show in the scenario with the best EquityMeasure, higher pollutant removal rates have been allocated to Sanandaj WWTP effluent and pollutant point source No. 7 (creek of landfill leachate) due to their greater contributions to Gheshlagh River contamination. Owing to high pollutant load effluents and unsuitable background conditions in Gheshlagh River, more specific studies show that the water quality index may not be improved over 0.22, no matter how much cost is incurred or equity is sacrificed.