The Pan-Tibetan Highlands are a temperate biodiversity hotspot, hosting the world’s most species-rich alpine flora. Extensive phylogeographic, biogeographic, and evolutionary studies have deepened our understanding of the evolution and underlying mechanisms of biodiversity in this region. Furthermore, recent advancements in our understanding of the geological history of this region have paved the way for interdisciplinary studies integrating geological, climatic, and biological processes to elucidate regional biodiversity. In this context, we incorporate the latest geological insights into the Pan-Tibetan Highlands, distinguishing the Tibetan Plateau, the Himalaya, and the Hengduan Mountains. We review the origin and evolutionary history of alpine plant diversity in the Tibetan-Himalayan-Hengduan region, as well as the underlying abiotic and biotic drivers that may influence diversification and reproductive isolation. Finally, we propose further exploration of the evolutionary histories and biotic interchanges between different mountain ranges at intercontinental or global scales, as well as investigations into the genetic mechanisms underlying adaptive strategies in alpine plants.