Abstract: This study, based on the natural foci of plague on the Qinghai-Xizang Plateau, explores the intricate interactions between humans, animals, and the environment. According to the "One Health" concept, this study systematically analyzes the transmission patterns of plague and its ecological drivers. The findings highlight that climate change and environmental degradation driven by human activities are reshaping the spatial dynamics of plague outbreaks by affecting the distribution of host animals and fleas (vectors). Building on the "One Health" concept, this study emphasizes the inseparable connection between human, animal, and environmental health, advocating for interdisciplinary collaboration. By integrating ecological monitoring, public health, and veterinary sciences, it proposes a comprehensive set of strategies, including enhancing plague monitoring and early warning systems, improving environmental management, and boosting public education and community involvement. These strategies offer new perspectives and approaches for addressing the risks of plague transmission.