Environmental monitoring of freshwater ecosystems faces significant challenges in detecting illicit wastewater discharges, which often remain unrecognized due to their intermittent nature and limited spatial footprint. This study presents a novel integrated strategy combining satellite remote sensing, Unmanned Aerial Vehicle (UAV)-based proximal sensing, and in situ measurements to enhance pollution detection in vulnerable aquatic environments. The methodology was applied to Lake Avernus (Italy), a volcanic lake historically affected by eutrophication and toxic cyanobacterial blooms. Landsat 8–9 thermal analysis revealed no detectable anomalies, reflecting the limitations of its coarse spatial resolution. Sentinel-2 multispectral imagery was then analyzed through spectral indices, band ratios, and reflectance signatures, revealing localized variations in surface reflectance and spatial heterogeneity in water optical properties. These satellite-derived anomalies guided targeted high-resolution UAV surveys. UAV-based thermal imaging revealed an elevated-temperature zone along the adjacent shoreline. In situ field screening flagged a candidate chemical anomaly at this location. The hierarchical framework demonstrates that satellite screening effectively identifies areas of concern, while UAV thermal imaging enables high-resolution localization of features invisible to satellite sensors, and in situ measurements provide essential ground-truth validation. This replicable, low-cost methodology offers a powerful tool for early warning, surveillance, and sustainable management of sensitive freshwater ecosystems.