Formulation of the problem. Modern global challenges and imbalances necessitate cooperation in new realities, change the interaction nature to counter global challenges by activating the most effective forms, methods, types and mechanisms of interaction and creating a new values philosophy and motivational guidelines for socio-economic interaction. The processes of socio-economic uncertainty of economic prospects in the context of global challenges require the formation of theoretical and methodological basis for the economic entities interaction. The aim of the research is formation of theoretical and methodological basis for economic entities socio-economic interaction in the context of modern global challenges. The subject of the research is theoretical aspect and methodological aspect of business entities socio-economic interaction in global challenges context. The methods of the research: historical method, methods of verification of theoretical positions (morphological analysis of the content and interrelation of categories, principles and laws, assessment of historical facts to theoretical hypotheses), methods of analysis and synthesis, induction and deduction, logical method (hypothetical and axiomatic approach), comparison method. The hypothesis of the research. In the context of global challenges, it is necessary to change the nature of interaction, for which it is necessary to form a theoretical and methodological basis for such interaction and determine the directions of necessary changes in interaction. The statement of basic materials. Within the epistemological field of research, the definitions of "interaction" as social, economic, philosophical, psychological and managerial categories are analyzed. The providing subsystems of business entities social and economic interaction in the conditions of global challenges are determined, among which the normative and legal, financial, logistical, personnel, informational, logistic, infrastructural, psychological, scientific, institutional, organizational supporting subsystems are singled out and characterized. Within the content (paradigmatic and methodological) basis of the research, it is proposed to distinguish the paradigmatic provisions of socio-economic interaction and the methodological basis of business entities socio-economic interaction research in the context of global challenges. The originality and practical significance of the research. The research of business entities socio-economic interaction in the context of global challenges includes four interrelated blocks – theoretical and explanatory basis of interaction, content (paradigmatic and methodological), applied and managerial basis of interaction, which complex covers possible interaction aspects. Conclusions and perspectives of further research. The article considers the theoretical and methodological basis of business entities interaction during global challenges, within which the implementation of the relevant logical blocks is proposed. Within the framework of further research it is planned to develop an applied basis of interaction, which will provide a diagnostic and prognostic field of socio-economic interaction in the context of global challenges and modeling of of business entities socio-economic interaction, as well as management basis of interaction of business entities, which will provide a sequence of management stages of the socio-economic interaction process and determine the interaction effectiveness in global challenges.