<p>This study presents a regional-scale hydrological balance for the upper and middle Veneto-Friuli Plain in northeastern Italy, covering approximately 8700 km². The analysis focuses on the period 2010–2022 and is aimed at quantifying the main recharge and discharge components, assessing the sustainability of water resources, and supporting informed management decisions. Inflows were assessed based on precipitation, surface runoff from rivers and springs, and water imports for human use, whereas outflows included river discharge, actual evapotranspiration, and groundwater withdrawals. Results indicate an annual water imbalance of 232.4 M m³. This imbalance could be due to either climate change or increased anthropogenic pressures, including groundwater overexploitation. To distinguish between these potential drivers, trend analyses were performed using a modified Mann-Kendall test on both precipitation and groundwater level data. No significant negative trends were observed in annual precipitation records from 185 meteorological stations. In contrast, declining trends were identified in 16 out of 100 monitored piezometers, suggesting that part of the imbalance, estimated at 37.2 M m³/year, may be attributed to groundwater depletion caused by overexploitation. The remaining 195.2 M m³/year is likely associated with unquantified groundwater inflow from adjacent fractured-rock aquifers. The findings highlight a substantial human footprint on the regional water cycle and emphasize the need for enhanced hydrological monitoring to reduce uncertainties in water balance estimates. This comprehensive water budget offers critical insights into water origin, use, and sustainability in the region, providing a scientific basis for adaptive and integrated water resource management strategies.</p>