This article examines interregional cooperation as a strategic instrument for reducing spatial differentiation in the Russian Federation. The relevance of the study is due to the persistence of significant regional disparities despite the prolonged use of equalization policies, highlighting the need for mechanisms that move beyond redistributive approaches toward coordinated development. The aim of the study is to identify governance mechanisms of vertical and horizontal cooperation and determine the factors that ensure their effectiveness in reducing spatial inequality. The central hypothesis is that the success of interregional initiatives depends on the presence of structured governance mechanisms capable of ensuring institutional synergy and overcoming administrative fragmentation. The research is based on a qualitative case study methodology. Four successful interregional projects are analyzed: the West Siberian Interregional Research and Education Center, the Oil and Gas Cluster of Tyumen Oblast, the Interregional Cluster for Nuclear Power Engineering, and subcontracting projects between the Chambers of Commerce and Industry of Arkhangelsk and Yaroslavl Oblasts. The empirical base includes official documents, analytical reports, expert assessments, and open-source materials. The results identify three key models of interregional cooperation: institutional, coordination, and network-based. The findings demonstrate that the most sustainable outcomes emerge from hybrid configurations combining vertical support (federal, institutional recognition, regulatory backing) with horizontal interaction (regional collaboration, business participation, and knowledge exchange). Key success factors include political commitment of regional leadership, reliance on established economic specialization, active involvement of private sector actors, the presence of dedicated project management structures, diversified financing mechanisms, and a results-oriented project approach. The scientific novelty lies in the systematization of governance models of regional cooperation and the empirical identification of success factors within the Russian spatial development context. The practical significance lies in the applicability of these findings for designing interregional initiatives and improving public policy instruments. The study concludes that interregional cooperation is an effective mechanism for reducing spatial differentiation when supported by institutional formalization, diversified, and coordinated stakeholder engagement. The greatest potential is observed in sectors critical to technological sovereignty, including the fuel and energy complex, nuclear power engineering, science and education. The study is limited by its focus on successful cases. Future research should examine unsuccessful projects, assess long-term impacts on regional inequality, develop quantitative evaluation tools, and explore the role of digital platforms in scaling cooperative models.