To solve the problems facing the regional industrial policy, it is necessary to integrate enterprises at the intersectoral and interregional levels, which makes it expedient to develop new organizational and economic models for combining economic agents on the basis of partnership and mutually beneficial cooperation, which allow coordinating the activities of industrial enterprises and attracting the resources of other actors of regional socio-economic systems. The scientific hypothesis formulated in the study is that formation and functioning of clusters based on the principles of ecosystem interaction, offering fundamentally different mechanisms for coordinating economic entities in a modern dynamic innovative environment, is an effective tool for economic policy in the context of systemic crises and for the purposes of sustainable development and achieving import independence of domestic industries. The author carried out a terminological analysis of the concepts of industrial cluster, industrial ecosystem and industrial symbiosis. It is substantiated that the cluster and symbiosis are specific concepts in relation to the industrial ecosystem. The cluster is a transitional form of the industrial ecosystem in terms of the evolution of the economic space, in turn, the industrial ecosystem is an organically and harmoniously arranged network of industrial clusters and/or symbioses. The synthesis of agglomeration and ecosystem approaches allows us to explore the cluster as a localized ecosystem, as well as to propose systemic mechanisms for integrating the regional space in the country based on optimizing the interaction of industrial cluster actors. In this context, the factors of collaboration and self-organization are considered as key in the processes of formation and evolutionary development of industrial clusters. Collaboration of actors is a reflection of the development of traditions of industrial cooperation, institutional and interpersonal trust, as well as non-hierarchical management. The article proposes a way to ensure compliance with the principle of self-organization of actors by formulating clear transparent rules for their entry into the cluster and functioning in it. The role of the reputational capital of enterprises and organizations in the processes of cluster self-organization as a localized ecosystem is analyzed. A list of parameters and indicators has been developed to assess the level of cluster maturity, taking into account modern challenges and trends. The main results of the study can become a theoretical and methodological basis for the formation of a policy to stimulate cluster development in Russian regions, stimulating industrial enterprises and ultimately affecting the economic growth and improving social indicators of enterprises, industries and the country as a whole. In further studies, it is planned to conduct an in-depth analysis of the ecosystem-agglomeration approach to the formation and development of clusters in order to operationalize it and introduce it into regional practice.