Rare and endangered species have narrow geographical distributions and are vulnerable to environmental changes. Studying the impact of future climate change on their distributions and identifying areas of high conservation priority are key to halting biodiversity loss. In this study, we combined a species distribution model with systematic conservation planning to simulate the suitable distributions of rare and endangered vascular plants and vertebrates in Inner Mongolia in the current and future (the 2050s), analyzed the vulnerability of species, and identified areas with high conservation priority. Currently, species richness (SR) of vascular plant was high in the Greater Khingan Mountains, and SR of vertebrates was high on the Hulunbuir Plateau, which are two species-rich areas. By 2050, 41.8% to 54.6% of vascular plants will have a reduced suitable distribution area, versus 46.8% to 51.1% for vertebrates. Vascular plant SR increased significantly in the Mu Us Desert, which became a new species-rich area. Vertebrate SR increased in western Inner Mongolia, but species-rich areas changed little. Species-rich areas are also potentially affected by future land use change, particularly in grassland, forest, and cropland areas with high SR. The current priority biodiversity conservation area covers 12.27 × 104 km2, of which 80.6% is located outside existing protected areas. By 2050, this percentage may increase to 83.4%. Our study revealed the potential pressure of existing protected areas in protecting biodiversity under future climate change, which helps decision-makers develop the most appropriate development strategies in advance to promote China's sustainable development.Graphical Abstract: