<p>Accurate exposure assessment is essential for understanding environmental health risks and for informing effective policy measures, particularly in areas where urban and industrial sources coexist. This study assessed long-term (2006–2019) air pollution exposure in the orographically complex Venafro Valley (southern Italy), an area characterized by multiple emission sources, to support an epidemiological investigation. To capture the spatial and source-specific heterogeneity of emissions, two complementary approaches, generally used independently, were combined. Diffuse pollution was characterized using fine particulate matter (PM_2.5) estimates derived from a satellite-based random forest model, while industrial contributions were evaluated through nitrogen oxides (NO_x) concentrations simulated by the Wrf/Calmet/Calpuff dispersion modelling system. Four exposure classes were defined for each pollutant using the “natural breaks” method to highlight relative spatial gradients rather than absolute concentration levels. The two methods revealed distinct exposure patterns. PM_2.5 peaked at the center of the valley, in the urban area of Venafro, largely influenced by traffic and biomass heating, whereas NOₓ hotspots were located near the industrial plants situated at the valley edges, close to the surrounding mountains. Overall, the findings highlight the need for integrated, multi-source approaches and additional monitoring stations to prevent biased exposure assessments. Although this study focuses on a specific area, the methodologies applied here may be transferable to other environmental or epidemiological contexts.</p>