Groundwater in hyper-arid regions as the southern parts of Egyptian Western Desert is considered as a key component for providing drinking water resources and supporting new national projects. Therefore, exploration programs and sustainable management strategies should be established by decision-makers for assessment of the groundwater resources for such areas. In the present work, the area south to Gilf Kebir plateau was considered as a case study for groundwater exploration using the integrative approach between regional-scale geological information with land-based geophysical measurements. This exploration program deals with the mapping of the Nubian Sandstone Aquifer System (NSAS) and delineation of subsurface structures and uplifts predominant in the basement bedrocks that have subdivided the area into sub-basins and controlled the aquifer recharge and groundwater potentialities in the Southern Western Desert. In order to achieve that target, land-based magnetic survey was applied along oriented long profiles, followed by Direct Current (DC) resistivity sounding to detect promising sites of groundwater. To fill the knowledge gap due to the absence of water wells in the region, the pervious remote sensing (Radarsat-1) and geological information were employed for picking four spots with different conditions and orientation to collect the land geophysical data. Geophysical results delivered that the region NE Jabal Kamel is promising for drilling due to the absence of igneous intrusions that act as natural barriers in the direction of water flow from the south, in addition to the great thickness of the sedimentary cover. On the other hand, some places as Eight Bells is characterized by shallow basement and basaltic intrusions with a depth of 30 m, while increase towards NE Jabal Kamal to reach about 500 m depth. The constructed geoelectrical and magnetic models give a sufficiently well-founded picture of subsurface structures and uplifts and their role in the groundwater potentialities in this arid region. The expected depth to water ranges from 69 to 81 m. The thickness of the proposed aquifer varies from 62 to 82 m with generally decreasing westwards due to igneous intrusions that interfering with the sedimentary section. While the chance of groundwater occurrence is nihilistic at the other three small areas Eight Bells, Jabal Kamel and Nosb Al-Amir.