Abstract: The Saihan Obo Ag-Pb-Zn polymetallic mining area in the southern segment of the Greater Khingan Range is located in the Huanggangliang-Ganzhuermiao metallogenic belt. Given the region’s frequent tectonic and magmatic activity and complex geological background, it is urgent to evaluate its deep prospecting potential. Building upon a systematic integration of historical exploration data, this study conducted specialized investigations into structural alterations. We employed isotope tracing and other experimental methods to elucidate the sources of ore-forming materials and the evolutionary history of ore-forming fluids. Furthermore, by integrating multi-source data from geology, geophysics, geochemistry, and drilling, this study comprehensively explored the district’s metallogenic regularities and prospecting potential. The results indicate that the deposit formed in an Early Cretaceous extensional tectonic setting. A composite mechanism governed its formation: deep, concealed small stocks provided heat and mass; strata served as ore-hosting layers; and faults acted as conduits and traps. Ore-forming materials derived predominantly from deep magmas, with minor crustal contamination. Ore-forming fluids evolved from early magmatic water to late-stage meteoric water, suggesting a medium-to-low-temperature hydrothermal filling type. Spatially, researchers have delineated over 100 mineralized and altered bodies and 44 ore bodies across the district, exhibiting typical characteristics of multi-directional mineralization, segmented aggregation, and structural control. Based on the coupling relationship between ore-controlling factors and anomaly information, a comprehensive prospecting indicator was established, centering on structural alteration zones, geochemical composite anomalies, and high-magnetic, medium-high polarization, and low-resistivity anomalies. Consequently, we identified three priority target zones for future exploration: the deep downward-dipping extension area of the Saihan Obo ore block, the medium-high temperature polymetallic metallogenic area in Liudigou, and the deep hydrothermal filling area in Xigou. These findings not only enrich the metallogenic theory of Ag-Pb-Zn polymetallic deposits in the southern Greater Khingan Range but also provide a crucial scientific basis and technical support for breakthroughs in deep prospecting in this region.