The contradictory integrity of globalization and regionalization processes in the modern world has been embodied in the formation of specific spatial areas – multiscale cross-border regions, whose functioning and development are determined both by the interactions between neighboring countries and by the totality of external geopolitical and geoeconomic circumstances. The article is devoted to the factors and features of cross-border processes and socio-economic development within one of the largest and most dynamic structures of modern Eurasia – the Greater Macro-Region of East Asia, embracing the northeastern and eastern territories of Russia, eastern China, Japan, and both Korean republics, Vietnam, and a number of other countries facing the seas of the northwestern Pacific. The integrity of this vast and very heterogeneous macro-region ranging from Chukotka to the Philippine Sea is based on relatively stable cross-border relations, which, in turn, are one of the determinants of these territories’ development. The role of geographical prerequisites (geographical location, climatic conditions, natural resources of land and sea) and geopolitical factors (geopolitical location and crossborder features) in the long-term development of this macro-region is assessed. It is shown that both favorable and negative prerequisites are associated with the cross-border nature of the integrated geosystems, including the marine ecosystems. Various types of cross-border regions with two-, three-, and four-link territorial segments belonging to different countries have been identified. The geopolitical potential of countries and regions is assessed, and the zones of geopolitical tension are revealed.