The gravity and magnetic data in the area south of the Qattara Depression has been investigated to define the structural framework of that area. Several techniques were applied to these data such as separation of regional and residual components, lineament analysis, tilt angle derivative, spectral analysis, and 2.5D gravity and magnetic modelling. The regional-residual separation was carried out using the Fast Fourier Transform to assess the sedimentary basins and the uplifted blocks. Lineament analysis was carried out to explain the main tectonic trends. The spectral analysis technique was applied to magnetic data to determine the depth to the basement surface along 21 profiles. 2.5D gravity and magnetic modelling along four profiles indicates that the area is formed from uplifted and down-faulted blocks of granitic and basaltic rocks. A tentative structural relief map was constructed to outline the main basins and uplifts. The results of this study show a thick sedimentary cover within the Abu Gharadig Basin exceeds 3000 m in most parts of the area under consideration. This sedimentary cover is thin in the south-western part within Faghur Basin. The structural pattern indicates that the area was affected mainly by: NE (Tibesti), ENE (Syrian Arc), N–S (East African), and NW (Suez) tectonic trends. The geothermal gradient was determined for six square areas. It has an average value of about 20.23 °C/km that can generate hydrocarbons within the outlined sedimentary basins. Because of the presence of thick clastic to carbonate rocks that were subjected to faulting and sufficient geothermal gradient to mature source rock; the Southern Faghur and Abu Gharadig basins can be considered as a promising region for further hydrocarbon exploration.