This systematic review of prospective studies examined whether psychological stress—conceptualised as cumulative stressful life events or perceived stress—is associated with cancer incidence. It was pre-registered in PROSPERO (IDCRD42020175681) and conducted following PRISMA guidelines. Methodological quality was assessed using the NIH Tool for Observational Studies, and the certainty of evidence was assessed using the GRADE tool. Hazard ratios were synthesised using random-effects meta-analyses. Nineteen studies were included, evaluating the effect of stressful life events (k=6) and/or perceived stress (k=15) on overall (k=3), breast (k=10), prostate (k=3), colorectal (k=2) and endometrial (k=1) cancer. Neither stressful life events nor perceived stress was consistently associated with cancer risk. Conflicting results emerged for perceived stress, including both protective and detrimental effects, particularly for breast and colorectal cancer. Most studies employed non-validated stress measures (k=12), assessed stress only once (k=17), and did not examine its impact comprehensively (k=11). The certainty of evidence was graded as very low. This review found no consistent evidence linking psychological stress to cancer risk. More high-quality prospective studies using comprehensive and validated measures of psychological stress and exploring potential moderators can help advance knowledge on the role of psychological stress in cancer incidence.