Semna area is located within the Golden Triangle district in the Central Eastern Desert of Egypt. The study maintains using multisource datasets of remote sensing, aero-spectrometry, aero-magnetic, and field investigations for unraveling the ambiguities associated with the alteration zones at the targeted area. Three remote sensing mapping techniques including; constrained energy minimization, linear spectral unmixing, and mineral indices, were adopted to delineate the alteration zones. The gamma-ray spectrometry data of K (%), K/eTh, K/ eU, and F-parameter enabled mapping the potassium-enriched localities as indication on possible potassic alteration zones. The surface and subsurface linear structural features were delineated from the digital elevation model and aero-magnetic data, respectively. The outcomes of all the implemented datasets were integrated using GIS overlay modeling, producing an integrated mineralization favorability/potentiality map. Eighteen localities with high potential for mineralization were highlighted. A field study was conducted to the investigated area during which, several alteration indicators were observed, including quartz veins, iron oxides staining, kaolinite, malachite, carbonate, and muscovite (sericite) alteration indicator minerals.