Uncertainty tolerance (UT) is integral to healthcare. Providers’ responses to medical uncertainty has ramifications on the healthcare system, the healthcare provider and the patient. Understanding healthcare providers’ UT, is important for improving patient-care outcomes. Understanding whether and to what extent it is possible to modulate individuals’ perceptions and responses to medical uncertainty, can provide insights into mechanisms for support for training and education. The objectives of this review were to further characterize moderators of healthcare UT and explore moderator influences on the perceptions and responses to uncertainty experienced by healthcare professionals. Framework analysis of qualitative primary literature was conducted on 17 articles, focusing on the impacts of UT on healthcare providers. Three domains of moderators were identified and characterized relating to the healthcare provider’s personal attributes, patient-derived uncertainty and the healthcare system. These domains were further categorized into themes and subthemes. Results suggest these moderators influence perceptions and responses to healthcare uncertainty across a spectrum ranging from positive to negative to uncertain. In this way, UT could be a state-based construct within healthcare settings and is contextually determined. Our findings further characterize the integrative model of uncertainty tolerance (IMUT) (Hillen Social Science and Medicine 180, 62–75, 2017) and provide evidence for the relationship between moderators and their influences on cognitive, emotional and behavioral responses to uncertainty. These findings provide a foundation for understanding the complex nature of the UT construct, add to theory development, and provide groundwork for future research exploring appropriate support for training and education in healthcare fields.