<p>Assessing waste load (WLA) configurations and implementing best management practices (BMPs) at a river-basin scale are essential for addressing water quality degradation. This study aims to assess and identify the most effective combinations of potential WLA programs and BMPs using the Soil and Water Assessment Tool (SWAT) for the Seymareh River basin (SRB) in Karkheh, Iran. After successfully calibrating and validating the SWAT model within the SRB, the model was employed to identify critical areas/units in the SRB prone to nutrient-related issues. Furthermore, it was used to evaluate the impacts of implementing combined WLA and BMP in these areas/units. The analysis focused on BMPs, exploring their attributes, operation, and maintenance costs. Further investigations were conducted to assess the effectiveness of BMPs in reducing nutrient loads at SRB, utilizing the SWAT. Based on the findings, vegetative filter strips, dry detention ponds, and decreased chemical fertilizer usage were chosen as BMPs to be implemented in SRB. Sensitivity analysis on the configurations and levels of wastewater treatment plants (WWTPs) revealed that among the 15-point-source units, the Kermanshah, Malayer, and Dinavar-Sahneh-Hersin municipal WWTPs, as well as the West Eslam-Abad and Sahneh-Kangavar aquaculture units, were the most significant contributors due to their high pollutant fluxes and strategic locations. Intensive sensitivity analysis on water resources conservation alternatives demonstrated that the annual TP loads in the SRB outflow were 6.48 × 10⁶ and 3.2 × 10⁶&#xa0;kg for the low-cost and environmentally-friendly alternatives, respectively. In comparison, the economic costs associated with these alternatives 500 × 10⁶ amounted to and 4800 × 10⁶ $, respectively.</p>