One of the most challenging tasks in mineral exploration is the search for mineralization in areas of complex tectonic setting with variable regolith. This study investigated the geological controls on lead–zinc (Pb–Zn) mineralization in the Es Souabaa anticline, northeast Algeria, considered a challenging region. To decipher evidence of Pb–Zn mineralization, a comprehensive and integrated study was conducted comprising the analysis of regional-scale remote sensing and geophysical data and local-scale geochemical data. A new enhancement step was applied to satellite images to overcome distortion resulting from regolith type, in addition to implementing multiple analysis methods to extract mineral spectral signatures and detailed surface geological/structural mapping. Moreover, the correlations among geophysical, geochemical analysis and subsurface mapped structural features were established to identify geophysical signatures indicative of the targeted mineral system. This study demonstrated the effectiveness of ASTER-derived mineral indices in mapping carbonate-hosted Pb–Zn deposits and identifying potential new mineralized zones. Structural feature analysis, as well as results of advanced analytical techniques of gravity and magnetic data, indicated that the area, which is characterized by transpressional tectonics, hosts Pb–Zn deposits primarily controlled by ENE–WSW-trending shear zones and fault intersections. Moreover, induced polarization, resistivity models, and surface/borehole sample analysis revealed significant variability in the distribution of ore bodies and reinforced the role of deep-seated faults as conduits for mineralized fluids. Shallow mineralized zones occur in the central region, while deep ones exist in the southern part at depths exceeding 190 m. The findings underscore the importance of structural mapping, data integration, and modeling for targeting Pb–Zn mineralization, reducing future exploration uncertainties in similar tectonic settings.