This paper gives a viewpoint on a controversial issue of transnational regional cooperation (TRC) in Eurasia covering the analysis of cooperation between Europe and the regions of Russia. By promoting the favorable regime of transnational regional cooperation, both sides become more effective in managing such common problems as mutual security, political, economic and environmental challenges; illegal immigration; drug- and human-trafficking; etc. What is needed for the successful development of TRC in Eurasian context? What factors make a crucial impact on the development of regional cooperation, whether it is further "inclusion" or "exclusion" of the regions from cooperation with European neighbors? Is it the geopolitical location of the regions that makes regional cooperation more feasible or are there other factors that influence the success of this process? How might the regulatory and administrative tools of central government facilitate or complicate this process? To answer these questions, the study attempts to re-conceptualize the theories of integration, Europeanization, and regionalism. Then, it addresses the role of ethnicity, economical development, and geopolitical factors in the establishment and development of transnational regional cooperation. It also investigates the importance of "domestic-policy factors" (reforms in the federal governments) in the development of TRC.