Extension-related within-plate Cenozoic volcanism in the central-western Mediterranean mostly occurs in three provinces: Veneto, Adria plate, i.e. African northern promontory; Iblei (Sicily), African lithosphere; and Sardinia, a drifted fragment of the European lithosphere. In Veneto (Paleogene) and Iblei (Neogene-Quaternary), transtensional rift volcanism developed as foreland reaction to collisional processes along the Alpine and Maghrebian chains respectively, generating prevailing basic magmas - from tholeiites to Na-alkali basalts and nephelinites. In Sardinia, the Pliocene-Quaternary volcanism - related to general tensional tectonics of the central Mediterranean – produced comparatively more potassic magmas from subalkaline basalts, alkali basalts/trachybasalts to basanites, locally associated with rhyolitic and phonolitic differentiates. Integrated petrogenetic study, based on incompatible element and Sr-Nd-Pb isotope systematics for the three volcanic provinces, leads to the following constraints: 1) the primary magmas, from tholeiites, alkali basalts to basanites and nephelinites, were generated by decreasing melting degrees of progressively deeper lithospheric mantle sources (ca. 30 to 100 km depth); 2) extensive and multiple enrichment processes by alkali-silicate metasomatizing components widely affected all mantle sources, which invariably require 5 – 10% metasomatic volatile-bearing phases, mainly amphibole for Veneto and Iblei, and phlogopite + amphibole for Sardinia; 3) a previously depleted lithospheric mantle (DM) is enriched by prevailing HIMU (with subordinate EMII) geochemical components in both Veneto and Iblean Provinces, whereas in Sardinia distinctly more potassic EMI signature predominates, in addition to HIMU; 4) in all the investigated provinces, the more alkaline deeper basic magmas (compared to sub-alkaline basalts) show relatively more marked HIMU signatures, also with involvement of carbonatitic components in the lowest lithospheric sources where nephelinites were generated. Mantle xenoliths associated to alkaline lavas of the three volcanic provinces, generally represent shallow portions of the lithospheric mantle column (< 40-50 km depth, i.e. in the Mechanical Boundary Layer, MBL) according to thermobarometric estimates and rheologic characteristics (e.g. grain size). Petrological data invariably indicate that these mantle xenoliths underwent a complex compositional evolution, characterized by depletions due to extraction of basic magmas (mostly occurring in the pre-Palaeozoic), and multiple metasomatic enrichments reflected in compositional variations of the constituent mineral phases, particularly pyroxenes, and the variable occurrence of pyrometamorphic textures and new phases, including glass + feldspar + amphibole + phlogopite. The resulting isotopic signatures conform well to those of their host magmas, being dependent on the variable contributions of the DM, HIMU, and EM components: a prevailing HIMU imprint is recorded for both Veneto and Iblean mantle materials, whereas a predominant EMI component, in addition to HIMU, is observed for the Sardinian mantle. A comparison at a circum-Mediterranean scale reveals that the geochemical features of Sardinia are also observed in the Cenozoic anorogenic magmas and associated mantle xenoliths located within the Variscan basement of centralwestern Europe. Peridotite massifs, tectonically emplaced during the Alpine orogeny, are similarly characterized (in addition to HIMU) by a prevalent EMI signature, which could thus have been active at least since the pre-Mid Mesozoic. By contrast, EMI signature is lacking in Veneto and Iblei, as well as in the mantle xenoliths and host alkaline lavas from other occurrences of the North African domain, where the HIMU component predominates. The widespread presence of HIMU in the European/North African domains may be related to the existence of a Cenozoic plume region extending from the eastern Atlantic to Central Europe and Central-Western Mediterranean, also suggested by the seismic tomographic data. Accordingly, the more recent HIMU metasomatizing agents rising from the convecting mantle appear to have been effectively accumulated in the lower lithospheric portions (i.e. Thermal Boundary Layer, TBL), whereas older metasomatic components (e.g. EMI for Europe) may have been better preserved in the upper, more rigid lithospheric mantle (i.e. MBL).