The Nefza mining district in Northern Tunisia comprises late Miocene (Serravallian toMessinian)magmatic rocks belonging to the post-collisional magmatism of the Mediterranean Maghreb margin. They are mainly made up of Serravallian granodiorite (Oued Belif massif), Tortonian rhyodacites (Oued Belif and Haddada massifs) and cordierite-bearing rhyodacites (Ain Deflaia massif) in addition to rare Messinian basalts. They are all characterized by LILE and LREE enrichment and strong enrichment in Pb and W. The Messinian basalts, which are also enriched in LILE, exhibit transitional characteristics between calc-alkaline and alkaline basalts. Geochemical (major and trace elements) and Sr, Nd and Pb isotopic compositions indicate that: (1) granodiorite is linked to the differentiation of ametaluminous calc-alkaline magma derived froma lithospheric enrichedmantle source and contaminated by old crustal materials; (2) rhyodacites result from the mixing of the same metaluminous calc-alkaline magma with variable proportions of melted continental crust. Cordierite-bearing rhyodacite, characterized by the highest 87Sr/86Sr isotopic ratios, is the magma comprising the highest crustal contribution in themetaluminous peraluminous mixing and is close to the old crustal end-member; (3) late basalts, transitional between the calc-alkaline and alkaline series, originated froman enrichedmantle source at the lithosphere asthenosphere boundary. In the Nefza mining district, magmatic rock emplacement has enhanced hydrothermal fluid circulation, leading to the deposition of polymetallic mineralizations (belonging to the Iron Oxide Copper Gold and the sedimentary exhalative class of deposits, among others). Magmatic rocks are also a source for the formation of lead (and probably other metals) in these deposits, as suggested by their Pb isotopic compositions. Magmatic rock emplacement and connectedmineralization events can be related to the Late Mio-Pliocene reactivation of shear zones and associated lineaments inherited from the Variscan orogeny.