People’s decisions to accept uncertainty are critical to career- and change-related decisions. Uncertainty acceptance can occur at any age or career stage, but the motivation and connection to the career stages remain undertheorized. Evolving conceptions of the “future of work” have accelerated through conditions emerging from significant shocks such as global pandemics and geopolitical tensions, changing conditions such as technology-enabled remote work, and steadily rising global aging. Given the importance of maintaining one’s livelihood and a general aversion to the stress-inducing uncertainty associated with career changes, the recent wave of career shifts underscores the limited conceptual tools scholars have with which to investigate and understand when, why, and how individuals are willing to accept and even instigate career-change uncertainties. Cognizant of the need to better identify, describe, and predict the origins and drivers of uncertainty acceptance, we utilize the person-environment fit perspective in theorizing a model whereby the desirability and feasibility of accepting uncertainty serve as a purposeful response to career dissonance, resulting from the fit, or misfit, individuals perceive concerning their existing career conditions and aspirations. We propose that individual and cultural factors moderate the desirability and feasibility of accepting uncertainty. We conclude by discussing the implications for both career and entrepreneurship literature.