Field geology, geochemical analyses and multi-sensor remotely sensed data of Landsat-8, ASTER and Sentinel-2 were used to detect various types of hydrothermal alteration and sulfide-gold mineralization in Neoproterozoic metavolcanic and gabbroic rocks from Darhib and El-Beida areas in the South Eastern Desert (SED) of Egypt. We also used RADAR data of Sentinel-1 using PCI Geomatica software to decipher the structural lineaments that control this mineralization. Different styles of disseminated to massive sulfide deposits include: 1) undeformed magmatic disseminated ores in Darhib gabbros, metavolcanic rocks and metabasic dykes; 2) deformed (remobilized) massive ores mostly of a magmatic-hydrothermal origin in Darhib tremolite talc rocks along E-W shear zones; 3) hydrothermal sulfide ores along El-Beida NW–SE shear zones. Cu-Zn massive ores represent the main sulfides in the Darhib silicified tremolite-talc rocks and meta-andesites, and occur as bands, veins and patches along Darhib E-W shear zones. Discontinuous occurrences of sulfide ores-bearing tremolite-talc rocks indicate that major shear zones act as structural controls on mineralization. Sulfide ores consist chiefly of chalcopyrite, sphalerite, pyrite and galena as well as minor covellite and bornite. These ores are highly concentrated along E-W striking Darhib shear zones and resulted from granite-derived hydrothermal fluids that form/and or accumulate sulfide minerals from the sulfide-bearing metavolcanic rocks around shear zones. Two stages of hydrothermal alterations are recorded in the Darhib talc mine including pre- (talcification, amphibolitization and carbonatization) and syn- (silicification and chloritization) sulfide ore alterations. Disseminated sulfide mineralization hosted in Darhib gabbros, metavolcanic rocks and metabasic dykes is of a magmatic origin, similar to Cu-Ni sulfide deposits hosted in gabbroic varieties in worldwide mafic–ultramafic intrusions. On the other hand, El-Beida gold-sulfide-bearing quartz and quartz carbonate veins are hosted in ferruginated and silicified metavolcanics/ metavolcaniclastic rocks along NW–SE shear zones (Najd Fault System trend). These are spatially associated with regional convergent structures (high-angle convergent wrench structures), suggesting orogenic gold type mineralization. The E-W with minor WNWESE shear zones in Darhib and NW-SE trending shear zones in El- Beida structurally controlled sulfides and gold mineralization in the SED of Egypt. El-Beida sulfide mineralization occurs as disseminated ores that consist mainly of pyrite, chalcopyrite, covelite and chalcocite with occasional occurrence of gold. The spatial occurrence of native gold in ferrigenous alteration zones indicates the role of iron in gold precipitation through buffering of gold-bearing complexes. Mineralogical and geochemical data of Darhib and El-Beida sulfide-bearing rocks indicate that they crystallized from depleted mantle sources in a back-arc basin setting, starting with the generation of arc-like volcanic rocks in a nascent BAB stage followed by the emplacement of plutonic equivalent of MORB/OIB-like rocks such as gabbroic intrusions in a mature BAB.