The definitions of interaction as a socio-economic category, the main categories of the methodological basis of socio-economic interaction are analyzed. The concept of "interaction" can be defined as a system of joint actions of several objects or entities, in which the action result of one of them affects the others. Global challenges lead to the need to change the interaction basis of economic entities due to the natural change of the general socio-economic and political-ideological formation of social development, which necessitates the definition and analysis of basic principles of business entities interaction in various global challenges. The basic principles of business entities socio-economic interaction in the context of global challenges are identified, among which the principle of commonality and feedback; openness and transparency; responsibility, the principle of professionalism and efficiency; social justice and corporate responsibility; concentrating on short-term planning and moving some issues from long-term to short-term planning; the principle of strategicity and changes in long-term development strategies; the principle of ethics; innovation and creativity of interaction; the principle of globality and global security; the principle of systematics and pluralism; tolerance and inclusion; integrity; the principle of changing established ties due to global political instability; the principle of global community; dynamism; laying a higher level of risk; compliance with environmental regulations and the principle of minimizing conflicts and institutionalizing compromises during interaction. In the context of global challenges and shocks, businesses are encouraged to abandon socio-economic determinism and resort to creative, innovative interaction because in the context of global challenges, creativity, innovation, knowledge, access to information, the ability to interact in socio-behavioral constraints are powerful engines of development of states, business entities and individuals. Creative interaction should be a constantly changing concept based on creative forms of cooperation, the result of which is not only survival in global shocks and imbalances, but also the activities of economic entities capable of generating impact on economic growth and development.