Groundwater exploration is the most promising way to overcome water scarcity in hyper-arid regions around the world. Due to the scarcity of hydrogeological information in these regions, groundwater exploration is a challenging issue requiring the joint application of satellite and land-based information to delineate the groundwater aquifers in such harsh environments. In this research, an integrative approach was undertaken for groundwater exploration in the southwestern corner of Egypt as one of the most hyper-arid regions in North Africa. To fill the knowledge gap in this large area, two high-resolution satellite gravity datasets (EIGEN-6C4 and TOPEX-1min) were employed in combination with land-based geophysical surveys for a better understanding of groundwater potentialities in terms of structural controls. Further, the approaches of high-pass filter, tilt angle derivative, and enhanced horizontal gradient amplitude were used to analyze EIGEN-6C4 dataset. Additionally, 2D and 3D models along with a high-pass filtered gravity map were constructed to provide the subsurface barriers and preferential groundwater flow pathways. Several NNE windows have been recognized, particularly to the east of Gabel Kamel along Uweinat-Aswan uplifting allowing groundwater flow along northeastern structural trends. To verify this assumption, land-based magnetic and DC resistivity sounding surveys were executed at two selected sites based on the interpretation of satellite gravity and remote sensing data. The resistivity and 2D magnetic modeling reveal the presence of remarkable sub-basins with sufficient saturated sedimentary cover. Ultimately, the review of the different datasets, including satellite gravity and land-based geophysical investigations, facilitated the geological interpretation for detecting the structural controls on the groundwater flow paths and produced satisfactory results at shorter time frames and lower costs compared to typical groundwater exploration in arid or hyper-arid regions of the same characteristics elsewhere.