Background: In today’s performance-oriented society, burnout symptoms, defined as consequences of chronic work stress, are an increasing problem. To counteract this development, the important aims are (1) to find protective and modifiable factors that reduce the risk of developing and harboring burnout symptoms and (2) to understand the underlying mechanisms. A phenomenon potentially furthering both aims is flow experience. Based on the earlier literature, we developed a psycho-physiological “Flow-Burnout-Model”, which postulates positive or negative associations between flow and burnout symptoms, depending on the prevailing situational and personal conditions. Methods: To test our Flow-Burnout-Model, we conducted a systematic literature search encompassing flow and burnout symptoms. Eighteen empirical studies met the inclusion criteria and were analyzed. Results: The findings of the systematic review as a whole suggest a negative association between flow and burnout symptoms, both cross-sectional and longitudinal. According to the findings from longitudinal studies, flow can be interpreted as a protective factor against burnout symptoms, and burnout symptoms can be interpreted as a factor inhibiting flow. In our conclusion, we maintain the assumption of a bidirectional association between flow and burnout symptoms in the Flow-Burnout-Model but modify the initially suggested positive and negative associations between flow and burnout symptoms towards a predominantly negative relationship. Discussion: Mindful of the heterogeneous findings of earlier studies, the resulting comprehensive Flow-Burnout-Model will lay the foundations for future hypothesis-based research. This includes physiological mechanisms explaining the relationship between flow and burnout symptoms, and likewise, the conditions of their longitudinal association.