Multiple geoscience databases as big data can be interpreted and understood by geologists using mineral system, including geological setting, metallogenic progress, and ore-bearing geological objects (e.g., porphyry, skarn, fault, fold, and stratum), and they can be used to extract exploration criteria based on GIS technology, weights of evidence (WofE), and concentration-area (C-A) methods for potential targets. In this paper, Luanchuan polymetallic district as a case study, the methodology and mineral system analysis based on the multiple datasets (geology, geophysics, geochemistry, remote sensing, and exploration engineering) were summarized as follows: (1) the databases’ construction using multiple geosciences involving the 1:25,000 scale gravity and magnetic dataset, 1:10,000 scale geologic map, and tens 1:5000 geological, geochemical, and geophysical cross-sections, more than 400 borehole datasets with 8000 assay; (2) Pb-Zn polymetallic deposit datasets involving magma-hydrothermal metallogenic model, ore-forming and rock-forming chronology, geochemistry and geophysics of stratum, and intrusion rocks; (3) GIS spatial analysis technology, 3D visualization technology, WofE, and C-A fractal methods were used to derive exploration criteria at different levels (the near surface (0 m), − 400 m, − 800 m); (4) potential target identification in vertical direction are compared and interactive interpreted to decease the uncertainty of the potential targets in the study area. The results show that the multiple geoscience datasets can be used to extract exploration criteria from surface to depth, the exploration criteria can be validated in the 3D geological model additional metallogenic model/genesis understanding (knowledge) and known polymetallic deposits of mineral system. The methodology can be used in the other mineral exploration districts or camps in the world.