Following the collapse of USSR, Russia was neglected from a serious attention towards Central Asia and Caucasus countries due to its own internal issues. Therefore a geopolitical vacuum emerged in this region and was followed by the activities of both regional players (including Iran, Turkey and the Zionist Regime); and transregional ones (the US and NATO). The conceptualization of “ Near Abroad” in Russia’ s national security document in 2015 and Putin’ s second presidency, as well as Russia’ s political, economic and social ties with Central Asian Republics, all led to Russia’ s serious attention once again towards the mentioned Republics, afterward referred to as Russia’ s “ backyard” or “ sphere of influence” . In order to scrutinize Russia’ s most important foreign policy challenges, using explanatory – analytical method, the present article attempts to answer the following question: Which factors are within Russia’ s most important foreign policy challenges for expanding its cooperation in Central Asia according to national security document and during Putin’ s second presidency? Using defensive realism, the author believes that NATO’ s expansion to East, terrorist activities in the region and United States unilateralism are Russia’ s most important foreign policy challenges in Central Asia.