The Arabian Nubian Shield (ANS) contains a variety of gold deposits in the form of veins and veinlets formed by hydrothermal fluids. Characterizing potential areas of hydrothermal alteration zones therefore provides a significant tool for prospecting for hydrothermal gold deposits. In this study, we develop a model of exploration for hydrothermal mineral resources in an area located in the ANS, Egypt, using multiple criteria derived from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), Landsat-Operational Land Imager (OLI), and Sentinel-2 data and field work through GIS-based fuzzy logic approach. The hydrothermal alteration zones (HAZs) map extracted from combining mineral indices, spectral bands, and ratios is consistent with observed argillic alteration zones around the mineralized veins. Combining HAZs and lineament density led to identification of six zones based on their mineralization potential, and provides a tool for successful reconnaissance prospecting for future hydrothermal mineral deposits. The detected zones are labeled as excellent, very high, high, moderate, low, and very low, based on their potential for Au production, and the predictive excellent and very high zones cover about 1.6% of the study area. This model also shows that target prospective zones are quartz veins controlled by NNW-SSE trending fracture/fault zones all crosscutting Precambrian rocks of the ANS. Field observations and petrographic and X-ray diffraction analyses were performed to validate the mineral prospective map and revealed that quartz veins consist of gold–sulfide mineralization (e.g., gold, pyrite, chalcopyrite, and sphalerite). Consistency between the high potential hydrothermal alterations zones (HAZs) and the location of gold mineralization is achieved.