In this study, diffuse and point source pollutant loads were evaluated using an Italian case study: the Nocella catchment, which has been subject to extensive monitoring. The Nocella catchment is located in Sicily (Italy) and has an area of about 60 km2. The river receives wastewater and stormwater from two urban areas drained by combined sewers. The two sewer systems, two wastewater treatment plants and a river reach were monitored during both dry and wet weather periods. Thereafter, an integrated catchment-scale model was applied to simulate point pollutant sources, i.e., pollution coming from the urban drainage system, and nonpoint pollutant sources, i.e., pollution coming from agricultural and wildlife activities. Different models were combined and long-term simulations were carried out in order to reconstruct the total pollutant loads discharged into the receiving water body and identify the roles of the different pollutant sources. This study demonstrates the complexity of water quality assessment in partially urbanised natural basins where neither point nor nonpoint sources can be neglected. Point sources are mainly responsible for acute oxygen demanding polluting impact during wet weather periods, and both point and nonpoint sources are responsible for the impact of nutrients on the receiving water body.