For 107 endemic mammal species in the Afro-Arabian region, Sahara-Sahel and Arabian Desert, we used ensemble species distribution models to: (1) identify the hotspot areas for conservation, (2) assess the potential impact of the projected climate change on the distribution of the focal species, and (3) assign IUCN threat categories for the focal species according to the predicted changes in their potential distribution range. We identified two main hotspot areas for endemic mammals: the Sinai and its surrounding coastal area in the East, and the Mediterranean Coast around Morocco in the West. Alarmingly, our results indicate that about 17% of the endemic mammals in the Afro-Arabian region under the current climate change scenarios could go extinct before 2050. Overall, a substantial number of the endemic species will change from the IUCN threat category "Least Concern" to "Critically Endangered" or "Extinct" in the coming decades. Accordingly, we call for implementing an urgent proactive conservation action for these endemic species, particularly those that face a high risk of extinction in the next few years. The results of our study provide conservation managers and practitioners with the required information for implementing an effective conservation plan to protect the biodiversity of the Afro-Arabian region.