The Nuocang Pb-Zn deposit is a newly discovered polymetallic skarn deposit in the southern Lhasa subterrane, western Gangdese, Tibet. The skarn occurs at the contact between the limestone of Angjie Formation and the Linzizong volcanic rocks of Dianzhong Formation (LDF), and the subvolcanic granite porphyry intruding those formations; the contact metasomatic skarn is well zoned mineralogically and texturally, as well as geochemically. The skarn minerals predominantly consist of an anhydrous to hydrous calc-silicate sequence pyroxene–garnet–epidote. The endoskarn mainly consists of an assemblage of pyroxene, garnet, ilvaite, epidote, and quartz, whereas the exoskarn is characterized proximal to distally, by decreasing garnet, and increasing pyroxene, ilvaite, epidote, chlorite, muscovite, quartz, calcite, galena, and sphalerite. Geochemical analyses suggest that the limestone provided the Ca for all the skarn minerals and the magmatic volatiles were the main source for Si (except the skarnified hornfels/sandstone, and muscovite-epidote-garnet-pyroxene skarn possibly from the host sandstones), with Fe and Mn and other mineralizing components. During the hydrothermal alteration, the garnet-pyroxene skarn and pyroxene-rich skarn gained Si, Fe, Mn, Pb, Zn, and Sn, but lost Ca, Mg, K, P, Rb, Sr, and Ba. However, the skarnified hornfels/sandstone, and muscovite-epidote-garnet-pyroxene skarn gained Fe, Ca, Mn, Sr, Zr, Hf, Th, and Cu, but lost Si, Mg, K, Na, P, Rb, Ba, and Li. The REEs in the skarn were sourced from magmatic fluids during the prograde stage. Skarn mineral assemblages and geochemistry indicate the skarn in the Nuocang deposit were formed in a disequilibrated geochemical system by infiltrative metasomatism of magmatic fluids. During the prograde stage, garnet I (And97.6Gro1.6) firstly formed, and then a part of them incrementally turned into garnet II (And64.4Gro33.8) and III (And70.22Gro29.1). The subsequent substitution of Fe for Al in the garnet II and III indicates the oxygen fugacity of the fluid became more reduced, then resulted in formation of significant pyroxene. However, the anisotropic garnet IV (And38.5Gro59.8) usually replaced the pyroxene. In the retrograde stage, the temperature decreased and oxygen fugacity increased, but hydrolysis increased with epidote, ilvaite, chlorite I, and muscovite forming with magnetite. The continuing decreasing temperature and mixing with meteoric water lead to Cu, Pb, and Zn saturation as sulfides. After the sulfides deposition, the continued mixing with large amounts of cold meteoric water would decrease its temperature, and increase its pH value (neutralizing), promoting the deposition of significant amounts of calcite and chlorite II. The geological, mineralogical, and geochemical characteristics of Nuocang skarn, suggest that the Nuocang deposit is of a Pb-Zn polymetallic type. Compared to the other typical skarn-epithermal deposits in the Linzizong volcanic area, it indicates that the Nuocang deposit may have the exploration potential for both skarn and epithermal styles of mineralization.