Highly managed Mediterranean river basins are experiencing severe environmental issues due to the overexploitation and degradation of both groundwater and surface water resources. Water resource managers face mounting concerns over the allocation of these limited resources, environmental quality, and planning amidst current and future climatic uncertainties. Understanding the hydrological components and water balance is crucial to addressing key questions related to water availability under various scenarios and future climatic conditions. In this study, the Soil and Water Assessment Tool (SWAT+) was utilized to develop an eco-hydrological model for the Cervaro river basin in Southern Italy. The objective was to evaluate baseline conditions and assess future climate projections towards the end of the 21st century. The model was driven by high-resolution data from Regional Climate Models (RCMs) under the Representative Concentration Pathways (RCP) 4.5 and RCP 8.5 scenarios. The baseline model was calibrated using observed streamflow data, ensuring a robust assessment of goodness-of-fit objective functions. Future hydrological responses were projected for the mid-century time scale. Our simulations revealed significant spatial variations in water fluxes, with an increase in potential evapotranspiration and a decrease in precipitation and surface runoff. These findings underscore the substantial impact that future scenarios may have on sustainable water resource management and the evaluation of climate change effects in this region. The insights gained from this study are essential for informing adaptive management strategies and policy decisions aimed at mitigating the impacts of climatic changes on water resources in highly managed Mediterranean river basins.