<p>A multi-indicator framework was developed to resolve multi-source pollution in highly urbanized rivers, demonstrated in the Qinhuai River Basin, Nanjing, China. Water quality index (WQI) stratification was integrated with dissolved organic matter (DOM) fluorescence components, hydrochemical ions, and conventional parameters and analyzed using positive matrix factorization (PMF). Correlation analysis further elucidated source compositions and interactions. DOM fluorescence profiles showed minimal variation across WQI levels, indicating limited discriminatory power of optical metrics alone. In contrast, K⁺, Na⁺, Ca²⁺, and Mg²⁺ concentrations increased with declining WQI and were strongly intercorrelated, reflecting the growing influence of wastewater inputs on water quality deterioration. PMF identified non-point sources predominantly in upstream reaches with relatively good water quality, point sources dominating degraded reaches with signatures consistent with domestic sewage, and internal sources that contributed more in summer due to sediment release and microbial decomposition. Strong correlations between nitrate, total nitrogen, and Na⁺ indicated wastewater treatment plant effluents as the primary nitrogen source. This integrated approach enables high-resolution source apportionment in urban rivers, providing a cost-effective and transferable tool for precision watershed management and transboundary water governance.</p>