This article provides the first comprehensive description and assessment of environmental changes in a unique natural transboundary region—South-Eastern Altai, which is located in the arid territories of Russia and Mongolia. This region of Asia is rightfully included in the high-mountain Third Pole (Roof of the World). In three key areas, Tsambagarav Massif (Mongolia), Mongun-Taiga Massif, and North-Chuya Ridge (Russia), the following are considered: (1) the latest dynamics of glaciers from the early 1960s (beginning of regular instrumental observations) to the present day; (2) climate change and land use systems; and (3) the characteristics of the biota and the causes of its dynamics. The article concludes with a consideration of (4) population adaptation models.