The Nuri deposit is the only Cu-W-Mo polymetallic deposit with large-scale WO3 resources in the eastern section of the Gangdese metallogenic belt, Tibet, China. However, the genetic type of this deposit has been controversial since its discovery. Based on a study of the geological characteristics of the deposit, this study presents mineralization stages, focusing on the oxide stage and the quartz-sulfide stage where scheelite is mainly formed, referred to as Sch-A and Sch-B, respectively. Through LA-ICP-MS trace element and Sr isotope analyses, the origin, evolutionary process of the ore-forming fluid and genesis of the ore deposit are investigated. Scanning Electron Microscope-Cathodoluminescence (SEM-CL) observations reveal that Sch-A consists of three generations, with dark gray homogenous Sch-A1 being replaced by relatively lighter and homogeneous Sch-A2 and Sch-A3, with Sch-A2 displaying a gray CL image color with vague and uneven growth bands and Sch-A3 has a light gray CL image color with hardly any growth band. In contrast, Sch-B exhibits a ‘core-rim’ structure, with the core part (Sch-B1) being dark gray and displaying a uniform growth band, while the rim part (Sch-B2) is light gray and homogeneous. The normalized distribution pattern of rare earth elements in scheelite and Sr isotope data suggest that the early ore-forming fluid in the Nuri deposit originated from granodiorite porphyry and, later on, some country rock material was mixed in, due to strong water-rock interaction. Combining the O-H isotope data further indicates that the ore-forming fluid in the Nuri deposit originated from magmatic-hydrothermal sources, with contributions from metamorphic water caused by water-rock interaction during the mineralization process, as well as later meteoric water. The intense water-rock interaction likely played a crucial role in the precipitation of scheelite, leading to varying Eu anomalies in different generations of scheelite from the oxide stage to the quartz-sulfide stage, while also causing a gradual decrease in oxygen fugacity (fO2) and a slow rise in pH value. Additionally, the high Mo and low Sr contents in the scheelite are consistent with typical characteristics of magmatic-hydrothermal scheelite. Therefore, considering the geological features of the deposit, the geochemical characteristics of scheelite and the O-H isotope data published previously, it can be concluded that the genesis of the Nuri deposit belongs to porphyry-skarn deposit.