The purpose of this article was to establish the interrelations and mutual influence of organizational culture transformation, national culture, and innovative business models’ formation under the COVID-19 pandemic. To achieve the study goal, a multi-stage comprehensive exploratory study based on primary information obtained by expert interviewing was implemented. The developed methodological approach was tested on the example of small and medium-sized enterprises in Russia and China. As a result of the conducted testing, the previously formulated hypotheses were fully proved. H1: the negative shock of the pandemic and the ensuing quarantine restrictions caused critical changes in the business environment, cancelling the relevance of previously effective business models. H2: the new business environment required enterprises to significantly transform their organizational culture. H3: under the conditions of shock changes in the business environment and forced transformation of organizational culture the main condition for the sustainable development of enterprises is innovative business models. Н4: implementation of innovative business models depends on both the business environment and the influence of national culture. The main obstacles to the implementation of innovative business models in small and medium-sized enterprises were also identified. The developed methodological approach can be used in the real sector of the economy by state organizations and non-state funds in the development of programs to assist small and medium-sized businesses in the COVID-19 pandemic. In addition, the study results may be of interest to academic researchers, suggesting empirically determined stable relationships (hypotheses H1, H2, H3, H4) between the transformation of organizational culture, national culture, and innovative business models’ formation to ensure sustainable development of enterprises under the COVID-19 pandemic and opening new promising directions for further research.