Satellite-based multi-sensor data coupled with field and microscopic investigations are used to unravel the setting and controls of gold mineralization in the Wadi Beitan–Wadi Rahaba area in the South Eastern Desert of Egypt. The satellite-based multispectral and Synthetic Aperture Radar (SAR) data promoted a vibrant litho-tectonic understanding and abetted in assessing the regional structural control of the scattered gold occurrences in the study area. The herein detailed approach includes band rationing, principal component and independent component analyses, directional filtering, and automated and semi-automated lineament extraction techniques to Landsat 8- Operational Land Imager (OLI), Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), Phased Array L-band Synthetic Aperture Radar (PALSAR), and Sentinel-1B data. Results of optical and SAR data processed as grayscale raster images of band ratios, Relative Absorption Band Depth (RBD), and (mafic–carbonate–hydrous) mineralogical indices are used to extract the representative pixels (regions of interest). The extracted pixels are then converted to vector shape files and are finally imported into the ArcMap environment. Similarly, manually and automatically extracted lineaments are merged with the band ratios and mineralogical indices vector layers. The data fusion approach used herein reveals no particular spatial association between gold occurrences and certain lithological units, but shows a preferential distribution of gold–quartz veins in zones of chlorite–epidote alteration overlapping with high-density intersections of lineaments. Structural features including en-echelon arrays of quartz veins and intense recrystallization and sub-grain development textures are consistent with vein formation and gold deposition syn-kinematic with the host shear zones. The mineralized, central-shear quartz veins, and the associated strong stretching lineation affirm vein formation amid stress build-up and stress relaxation of an enduring oblique convergence (assigned as Najd-related sinistral transpression; ~640–610 Ma). As the main outcome of this research, we present a priority map with zones defined as high potential targets for undiscovered gold resources.