Pathfinder elements associated with the exploration footprint of the McArthur River unconformity-related U deposit include U, radiogenic Pb, V, Ni, Co, Cu, Mo, As, Zn, and rare earth elements. In this study, the mineralogical and paragenetic context for their occurrence was established by integrating in situ mineral chemistry and laser ablation mass spectrometry chemical mapping of interstitial assemblages, detrital grains, and cements with whole-rock analyses of drill core samples from the diagenetically altered background and the hydrothermally altered sandstone host rocks. Diagenetically altered background sandstones contain a matrix assemblage of illite and dickite, with trace to minor aluminum-phosphate-sulfate (APS) minerals, apatite, and Fe-Ti oxide minerals. Aluminum-phosphate-sulfate minerals account for the majority of the Sr and light rare earth element concentrations, whereas early diagenetic apatite, monazite, and apatite inclusions in detrital quartz and detrital zircon contribute significant U and heavy rare earth elements to samples analyzed with an aggressive leach (partial digestion) such as aqua regia. Hydrothermally altered sandstone host rocks also contain variable assemblages of Al-Mg chlorite (sudoite), alkali-deficient tourmaline, APS minerals, kaolinite, illite, Fe-oxide, and sulfide minerals. Late pre-mineralization chlorite accounts for a significant portion of the observed Ni concentrations, whereas Co, Cu, Mo, and Zn occur predominantly in cryptic sub-micron sulfide and sulfarsenide inclusions within clay mineral aggregates and in association with Fe-Ti oxides. Elevated concentrations of U were observed in cryptic micro-inclusions associated with sulfides in quartz overgrowths, with Fe-Ti oxide micro-inclusions in kaolinite, and in post-mineralization Fe-oxide veins. The distribution of pathfinder elements throughout the deposit footprint appears to be less related to the primary dispersion of alteration minerals from the hydrothermal system than to the secondary dispersion of elements post-mineralization. Their occurrence throughout pre-, syn-, and post-mineralization assemblages further demonstrates the limitations to defining geochemical footprints from pathfinder element concentrations expressed in lithogeochemical data sets without structural, lithological, and mineralogical context.