The increasing demand for freshwater supplies and the effects of climate change in arid and hyper-arid regions are pushing governments to explore new water resources for food security assurance. Groundwater is one of the most valuable water resources in these regions, which are facing water scarcity due to climatic conditions and limited rainfall. In this manuscript, we provide an integrated approach of remote sensing, geographic information systems, and analytical hierarchical process (AHP) to identify the groundwater potential zone in the central Eastern Desert, Egypt. A knowledge-driven GIS-technique-based method for distinguishing groundwater potential zones used multi-criteria decision analysis and AHP. Ten factors influencing groundwater were considered in this study, including elevation, slope steepness, rainfall, drainage density, lineament density, the distance from major fractures, land use/land cover, lithology, soil type, and the distance from the channel network. Three classes of groundwater prospective zones were identified, namely good potential (3.5%), moderate potential (7.8%), and poor potential (88.6%) zones. Well data from the study area were used to cross-validate the results with 82.5% accuracy. During the last 8 years, the static water level of the Quaternary alluvium aquifer greatly decreased (14 m) due to excessive over pumping in the El-Dir area, with no recorded recharges reaching this site. Since 1997, there has been a noticeable decline in major rainfall storms as a result of climate change. The current study introduces a cost-effective multidisciplinary approach to exploring groundwater resources, especially in arid environments. Moreover, a significant modern recharge for shallow groundwater aquifers is taking place, even in hyper-arid conditions.