The Bubin Cu-Pb polymetallic deposit in Gilgit-Baltistan, Pakistan, is a well-known vein-type ore deposit located in the Kohitan-Ladakh island arc. Due to its significant economic importance as the most important deposit type in the Kohistan-Ladakh island arc, a comprehensive study on its ore genesis, fluids evolution, and genetic classification not only shed new light on our understanding the formation of such polymetallic deposit at a typical intra-oceanic arc, but also of help for the mineral exploration. Here, we present the results from electron probe micro-analyzer, fluid inclusions, Raman spectroscopy, and isotopic studies (O-H-S-Pb) to gain insights into the source of ore-forming fluids and materials, as well as the genetic-type and mechanism of ore precipitation for the Bubin deposit. The mineralization processes were divided into three main stages: Stage I (quartz-pyrite), Stage II (quartz-sulfide), and Stage III (quartz-carbonate). Stage II further comprised two sub-stages: IIa (quartz-chalcopyrite-magnetite) and IIb (quartz-galena-fahlore). The ore-forming fluids exhibited high to moderate temperatures (154–540 °C) and varying salinities (0.35–44.30 wt% NaCl) throughout the stages. Stage I fluids displayed critical behavior with high temperature and low salinity, and their isotopic signatures suggested a magmatic origin. Subsequently, the ore-forming fluids gradually evolved from primary magmatic origin to the mixing of meteoric water, as demonstrated by oxygen and hydrogen isotopic values (δ18Ofluid = -1.34 to 6.29 ‰, δD = -112.4 to −76.1 ‰). The δ34S values (-2.92 to 6.52 ‰) and Pb isotopic ratios (208Pb/204Pb = 39.06 to 40.93, 207Pb/204Pb = 15.72 to 15.99, and 206Pb/204Pb = 19.44 to 20.80) suggested a deep magmatic source for the ore-forming fluid, with metals primarily derived from the upper crust, likely associated with the Ladakh Batholith. Fluid boiling and maxing are the dominant mechanisms for ore mineral precipitation. Additionally, the high to moderate temperature and salinity, presence of solid-bearing and vapor rich inclusions, a Co/Ni ratio > 1, the Ni-As-Co diagram, and O-H-S-Pb isotopic evidence collectively support the classification of the Bubin Cu-Pb polymetallic deposit as an intrusion-related porphyry-style magmatic hydrothermal deposit.