Abstract: The Xiongwu tectonic belt is a critical ore-controlling structure for Au-U polymetallic mineralization in Southwestern Guizhou. Significant progress has been made in Au and U exploration has been achieved in recent years. Through an integrated analysis of structural characteristics, Au-U polymetallic mineralization features, and their genetic relationships, this study reveals the three-level hierarchical control system, including anticline, major faults, interlayer detachment zones, along with secondary fracture zones and dense fissure zones, plays a clear role in controlling mineralization. The mineralization exhibits a prominent "Anticline + Fault + Structural Alteration Body" emplacement pattern. Ore bodies are primarily hosted within two metallogenic systems, interlayer detachment structures and fault zones. Based on these findings, two metallogenic models have been established, including lateral injection, migration, and metasomatic emplacement of ore-forming fluids, as well as ascending metasomatic emplacement. Furthermore, by synthesizing geological structures and geochemical data, several prospective areas for Au-U polymetallic exploration have been identified, including Songmaoping-Luojiabao and Dajishan-Huangnibao-Tiechangwan. This study provides novel insights and directions for the new round of the Mineral Exploration Breakthrough Strategy, offering significant guidance for expanding exploration achievements in Au polymetallic deposits.