Climate change and increasing water demand threaten water security in strategic high-Andean reservoirs by altering seasonal water availability, increasing evaporative losses, and intensifying pressure on regulated storage. This study assesses the hydrological vulnerability of the Pañe Reservoir, Arequipa, Peru, under CMIP6 scenarios SSP2-4.5 and SSP5-8.5 and three water-demand trajectories projected to 2100. A reservoir-scale water-balance model was calibrated using a genetic algorithm with CHIRPS precipitation and ERA5-Land temperature data, achieving satisfactory performance in calibration (NSE = 0.886; $R^2$ = 0.907) and validation (NSE = 0.888; $R^2$ = 0.891). Climate projections from MPI-ESM1-2-LR, EC-Earth3-Veg-LR, and EC-Earth3 were bias-corrected using Quantile Delta Mapping. Under baseline demand, active storage maintains positive trends of +1.3 $\times {10}^6$ to +2.2 $\times {10}^6$ m³/decade; however, a 100% demand increase produces negative trends of up to −2.8 $\times {10}^6$ m³/decade under SSP2-4.5. Effective precipitation increases by +0.123 and +0.283 mm/day under SSP2-4.5 and SSP5-8.5, respectively, while Rx5day and Rx10day rise by +5.43/+8.78 and +12.13/+19.42 mm/decade. These trends suggest greater wet-season concentration of water inputs, but not necessarily improved dry-season security under rising demand. Reservoir warming reaches +0.60 °C/decade under SSP5-8.5, which may increase evaporative losses and could create conditions more favorable to water-quality deterioration. Overall, future vulnerability in the Pañe system reflects the imbalance between increasing withdrawals and the reservoir’s capacity to regulate highly seasonal high-Andean inflows, highlighting the need for demand control, loss reduction, bofedal protection and complementary wet-season storage.