Background <p>Registered professional nurses frequently encounter a highly demanding and challenging work environment, leading to high psychosocial allostatic load. This poses a risk to the psychosocial and physical well-being of nurses, influences the quality of patient care, and leads to negative consequences for the hospital group. This systematic review aimed to identify and evaluate the most pertinent literature to gain a deeper understanding of the causes, mechanisms and impact of psychosocial allostatic load experienced by nurses in the workplace.</p> Methods <p>Articles were selected from several databases, including Academic Search Complete, the American Psychological Association’s (APA) PsycArticles, APA PsycINFO, Cumulated Index in Nursing and Allied Health Literature (CINAHL), Health Source Nursing, Medical Literature Analysis and Retrieval System Online (Medline) and SocIndex. In total, 16 articles that met the search criteria were included in the final review.</p> Results <p>The findings indicated the most important causes of allostatic load to be individual existing factors as well as chronic exposure to long-term stressors at work. Mechanisms of allostatic load were defined as the successful adaptation to workplace stressors through allostasis, and if not effectively done, can result in psychosocial allostatic overload.</p> Conclusion <p>Prolonged exposure to allostatic load was implicated to ultimately alter the cognitive, behavioural, and affective systems of nurses. The findings were synthesised into a psychosocial allostatic load model to enhance the understanding of psychosocial allostatic load in nursing practice and support social workers in developing a psychosocial intervention programme.</p>