Demingding is a promising porphyry Mo-dominated deposit recently discovered in the eastern Gangdese metallogenic belt in Tibet, China. We present zircon U-Pb-Lu-Hf isotopic studies, as well as geochemical data of the late monzogranites and the prior rhyolites from the Demingding porphyry deposit to uncover their origin and geodynamic mechanism. Zircon U–Pb dating yielded precise crystallization ages of 17.3 ± 0.6 Ma (MSWD = 2.5) and 186.5 ± 3.0 Ma (MSWD = 2.0) for monzogranite and rhyolite, respectively. The monzogranite is characterized by high-K calc-alkaline, adakitic affinities, and positive zircon εHf(t) values (+0.9∼+5.6, avg.+3.1) with TDM2 (0.73–1.04 Ga), while the rhyolite has εHf(t) values of (+2.1∼+7.3, avg.+5.2) and TDM2 of (0.76–1.09 Ga) similar to the monzogranite. Our results suggest that the Demingding porphyry Mo (Cu) deposit is related to magma generated from the Neo-Tethyan oceanic subduction. The subsequent monzogranite porphyry was likely formed by the remelting of previously subduction-modified arc lithosphere, triggered by continental collision crustal thickening in Miocene. The lower positive εHf(t) values of monzogranites suggest minor inputs from the Mo-rich ancient crust, suggesting that Mo favors the silicate melt. Such magmatic events and special metallogenesis typify intracontinental processes and porphyry copper deposits, which are normally confined to oceanic subduction and Cu-dominated style, thereby making the continental setting and Mo-dominated style of Demingding exceptional and possibly unique.