Groundwater is a critical resource in arid regions such as Khamis Mushayt, located in southwestern Saudi Arabia, where surface water availability is limited. This study integrates various geospatial and environmental datasets to delineate groundwater potential zones (GWPZs) using Geographic Information Systems (GISs) and remote sensing (RS) techniques. Key parameters considered include lithology, slope, drainage density, precipitation, soil type, and vegetation index (NDVI). The influence of each theme and subunit/class on groundwater recharge was evaluated by weighted overlay analysis, including previous studies and field data. The results reveal three distinct groundwater potential zones: poor, moderate, and good. Areas with good groundwater potential account for 8.2% of the study area (16.3 km2) and are predominantly located in the eastern and central parts of the study area, in valleys and low-lying regions with permeable geological formations such as alluvial deposits, supported by higher drainage density and favorable precipitation. Conversely, poor-potential zones represent 27.6% (54.50 km2), corresponding to areas with steep slopes and impermeable rock formations. Moderate-potential zones include places where infiltration is possible but limited, such as gently sloping terrain or regions with slightly broken rock structures, and account for 64.2% (127.0 km2). Validation using existing well data demonstrates strong agreement between the identified potential zones and actual groundwater availability. These findings provide a strong framework for sustainable water resource management, urban planning, and agricultural development in Khamis Mushayt and similar arid regions.