The mining district of Nefza-Sejnane (Tunisia) encloses numerous ores and raw material deposits, all formed in relation with successive Fe-rich fluids of meteoric and/or hydrothermal origins. Here, for the first time in Tunisia, (U-Th)/He ages were obtained on supergene goethite from various localities/deposits of the district highlight direct dating of significant weathering episodes during late Tortonian and late Pleistocene. These weathering events are most likely associated with favorable conditions that combine (i) wet climate displaying sufficient meteoric water/fluid; and (ii) regional exhumation, due to large-scale vertical lithospheric movements enhancing the percolation of fluids. Matched with previous works, these results refine the stratigraphic frame for the polymetallic mineralization and clay deposits in the district, confirming the influence of meteoric fluids circulation during the late Cenozoic. As a consequence of the new (U-Th)/He data, we moreover propose a taxonomic and stratigraphic revision of the well-known mammalian fauna from the Fe-rich Douahria locality, suggesting an early Tortonian age for the fossils, i.e., prior to the first episode of meteoric event in the area.