Irrigation-led farming system intensification and efficient use of ground and surface water resources are currently being championed as a crucial ingredient for achieving food security and reducing poverty in Nepal. The potential scope and sustainability of irrigation interventions under current and future climates however remains poorly understood. Potential adaptation options in Western Nepal were analyzed using bias-corrected Regional Climate Model (RCM) data and the Soil and Water Assessment Tool (SWAT) model. The RCM climate change scenario suggested that average annual rainfall will increase by about 4% with occurrence of increased number and intensity of rainfall events in the winter. RCM outputs also suggested that average annual maximum temperature could decrease by 1.4 °C, and average annual minimum temperature may increase by 0.3 °C from 2021 to 2050. Similarly, average monthly streamflow volume could increase by about 65% from March–April, although it could decrease by about 10% in June. Our results highlight the tight hydrological coupling of surface and groundwater. Farmers making use of surface water for irrigation in upstream subbasins may inadvertently cause a decrease in average water availability in downstream subbasins at approximately 14%, which may result in increased need to abstract groundwater to compensate for deficits. Well-designed irrigated crop rotations that fully utilize both surface and groundwater conversely may increase groundwater levels by an average of 45 mm from 2022 to 2050, suggesting that in particular subbasins the cultivation of two crops a year may not cause long-term groundwater depletion. Modeled crop yield for the winter and spring seasons were however lower under future climate change scenarios, even with sufficient irrigation application. Lower yields were associated with shortened growing periods and high temperature stress. Irrigation intensification appears to be feasible if both surface and groundwater resources are appropriately targeted and rationally used. Conjunctive irrigation planning is required for equitable and year-round irrigation supply as neither the streamflow nor groundwater can provide full and year-round irrigation for intensified cropping systems without causing the degradation of natural resources.