Witnessing a dramatic change in business globalization and struggling with the iterative outbreak of Covid-19, entrepreneurship has been shifting from resource-driven to innovation-driven. Uncertainty theory can help us understand how startups are born, survive, and develop in such a complex environment. Uncertainty theory plays a fundamental and supporting role in the theoretical system of innovation-driven entrepreneurship. Enterprises need to seek certainty in the uncertainty and bridge continuity in the discontinuity. By reviewing the development of uncertainty theory and its application in the field of entrepreneurship, this chapter attempts to clarify the role of uncertainty theory in innovation and entrepreneurship in a complex environment, especially in the innovation-driven entrepreneurship literature.