This entry attempts to unpack how the entrepreneurial cognition and entrepreneurial orientation (of enterprise players) interact for tackling adversity. Drawing on cognitive theories of possibilistic thinking, adaptive cognition, and collective cognition, I advance how these mechanisms affect the entrepreneurial orientation of innovativeness, risk-taking, and proactiveness of entrepreneurial orientation. The interaction of the entrepreneurial cognition and orientation becomes the proposed “entrepreneurial cognition in adversity” that can profoundly trigger the enterprise process of idea generation, value offering development, and market product creation in times of adversity. Using a case illustration, the related phenomena were mapped for illuminating how a social enterprise tackled the adversity of COVID-19. This entry contributes by providing a cognitive framework that led to the adversity-driven innovation practice during the grand challenge of pandemic.