Multispectral remote sensing data provided valuable information for hydrothermal minerals exploration. In this article, Landsat-8 Operational Land Imager (OLI) and Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data were processed and analyzed using band ratio and principal component techniques to demarcate areas of hydrothermal mineral resources by highlighting the most influenced zone of hydrothermal alteration (high-grade) in Egypt. The area is a part of the Arabian-Nubian Shield, covering 1068 km2, and comprises wide varieties of Pre- and Pan-African rock assemblages. Preparing and integrating thematic layers consisting of the grade of hydrothermal intensity in a GIS technique supported generating a hydrothermal mineral predictive map (HMPM) using a multi-criteria decision-making technique. The plausible zone of very high mineral resources covers about 6.57 %. Analysis of ASTER data revealed that this zone is reliable with phyllic and argillic minerals and iron-oxides. The results of OLI data helped in demarcating potential areas of hydrothermal alteration areas (Al–OH) mixed with iron oxides. Field observations and investigations enabled the validation of the HMPM. The spatial distribution of hydrothermal zones throughout the study was reliable to that observed in the mine areas. Field and ore microscopic examination verified the existence of Au-sulfide minerals connected with hydrothermal alteration zones (HAZs) in different areas e.g., Abu-Marawat, Gidami, Semna, Abu-Gaharish, and Hamama mines. Overall, integrating multi-spectral data through overlay analysis techniques can provide valuable information about hydrothermal mineral resources in an accurate and cost-effective approach.