Nurses have been found to experience higher levels of stress-related burnout compared to other health care professionals. Despite studies showing that both job satisfaction and burnout are effects of exposure to stressful working environments, leading to poor health among nurses, little is known about the causal nature and direction of these relationships. The aim of this systematic review is to identify published research that has formally investigated relationships between these variables. Six databases (including CINAHL, COCHRANE, EMBASE, MEDLINE, PROQUEST and PsyINFO) were searched for combinations of keywords, a manual search was conducted and an independent reviewer was asked to cross validate all the electronically identified articles. Of the eighty five articles that were identified from these databases, twenty one articles were excluded based on exclusion criteria; hence, a total of seventy articles were included in the study sample. The majority of identified studies exploring two and three way relationships (n = 63) were conducted in developed countries. Existing research includes predominantly cross-sectional studies (n = 68) with only a few longitudinal studies (n = 2); hence, the evidence base for causality is still very limited. Despite minimal availability of research concerning the small number of studies to investigate the relationships between work-related stress, burnout, job satisfaction and the general health of nurses, this review has identified some contradictory evidence for the role of job satisfaction. This emphasizes the need for further research towards understanding causality.