Background: Mental fatigue is a common occupational psychological issue among knowledge workers, which can easily lead to various psychological disorders and major accidents. However, the etiology and pathogenesis remain unclear. Objective: This article aims to review the research progress on mental fatigue among knowledge workers, focusing on understanding the hazards, manifestations, theoretical models, and intervention strategies. Methods: A thorough search was conducted on PubMed, Web of Science, EBSCOhost (CENTRAL, SPORTDicus), and CNKI using the keywords "knowledge workers + mental fatigue" or "intellectual workers + mental fatigue", as well as on Google Scholar and reference sources for grey literature. Results: A total of 50 papers were included. Previous literature indicates that mental fatigue among knowledge workers occurs on the basis of long-term, singular high-intensity work tasks causing physical fatigue, manifesting as feelings of psychological exhaustion and boredom, involving multiple aspects of cognition, emotion, and function. There are various theoretical models of mental fatigue, with the widely cited cognitive resource theory, self-regulation theory, underload theory, and motivation control theory. Each theoretical model focuses on a specific aspect and fails to reveal the complete psychological mechanism of mental fatigue. Interventions include mindfulness training, music relaxation, physical activity, and appropriate rest. Conclusion: Mental fatigue poses a significant threat to knowledge workers, but its psychological mechanism remains unclear. Although there are various intervention methods, they have failed to completely eliminate mental fatigue.