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[Display omitted] • SEDE genesis is most plausible for the first episode of mineralization in the Zhaxikang and Keyue deposits. • A genetic relationship must exist between the Zhaxikang and Keyue deposits. • The Zhaxikang and Keyue deposits have the same metal origins and experience similar ore formation and ore-forming fluid evolution. • Zn–Cd isotopes have the potential to apply in ore deposit research and mineral exploration. The Keyue Sb–Pb–Zn–Ag deposit is a medium-sized deposit near the super-large Zhaxikang Sb–Pb–Zn–Ag deposit within the North Himalayan Metallogenic Belt (NHMB). These two deposits, separated only by a regional NS-trending normal fault with strike-slip properties, have similar ore-forming elements and mineral associations, ore characteristics, ore paragenetic sequence, wall rocks, and H–O–S–Pb isotopic and fluid inclusion characteristics. Herein, we establish Zn–Cd isotopic connections between these two proximal ore deposits. As a means to draw comparisons, we conducted Zn–Cd isotopic research of the Keyue deposit to compare it with that of the Zhaxikang deposit. Both the δ66Zn and δ 114/110Cd values of sphalerite from the Keyue deposit display a temporally decreasing trend from stage 2 (δ66Zn: 0.15‰–0.58‰, average value = 0.29‰; δ 114/110Cd: –0.23‰ to 0.38‰, average value = 0.05‰) to stage 3 (δ66Zn: –0.28‰ to 0.12‰, average value = –0.06‰; δ 114/110Cd: –0.38‰ to –0.32‰, average value = –0.35‰), which was also found in the Zhaxikang deposit. A simple three-phase separation distillation models this temporally decreasing trend, which resulted from the Zn–Cd isotopic fractionation that is most likely related to vapor–liquid-solid dynamics of ore-forming fluid. This distillation model was further augmented by the general geochemical characteristics and fluid inclusion data. A congruence among several geological and geochemical evidence points to the genetic relationships between these two ore deposits that have the same metal origins and experience similar ore formation processes. A three-phase separation model has been established to imitate this evolution, which reveals substantial exploration potential for Zn–Cd at depths below 4100 m within the Zhaxikang orefield. In summary, Zn–Cd isotopes have the potential to trace metal sources, monitor fluid evolution, constrain ore formation, and provide insights into mineral exploration. [ABSTRACT FROM AUTHOR]