Uranium exploration plays a pivotal role in meeting global energy demands and advancing nuclear technology. This study presents a comprehensive approach to uranium exploration in the Gebel Duwi area of the Central Eastern Desert of Egypt, utilizing remote sensing and airborne gamma-ray spectrometric data. Multispectral remote sensing techniques, including Principal Component Analysis (PCA), Minimum Noise Fraction (MNF), and Band Ratioing (BR), are employed to identify lithological units and hydrothermal alteration zones associated with uranium deposition, such as iron oxides, argillic, propylitic, and phyllic alterations. Additionally, airborne gamma-ray spectrometry data provide insights into the spatial distribution of radioelements, including uranium (eU), thorium (eTh), and potassium (K), as well as radioelement ratios (eU/eTh, eU/K, and eTh/K). The uranium migration index map (eU-(eTh/3.5)) and the F-parameter map (K*(eU/eTh)) have been generated to investigate the movement of uranium within various geological zones and characterize anomalous uranium concentrations. Statistical analyses, including mean (X), standard deviation (S), and coefficient of variability (C.V.), are conducted to identify uranium-rich zones. The integration of these datasets enables the generation of a uranium potential map highlighting areas of elevated concentrations indicative of uranium mineralization. Field observations and mineralogical analyses of collected samples validate our findings, confirming the presence of minerals associated with uranium mineralization in mapped high-potential areas. The significance of minerals like Fe-Chlorite, Fe-Mg-Chlorite, ferrihydrite, goethite, calcite, muscovite, dolomite, actinolite, vermiculite, and gypsum in indicating potential uranium mineralization processes underscores the importance of our results.