<p>Evidence from experimental studies suggests that pain may influence cancer development. We conducted a systematic review (registration osf.io/ms437) of the epidemiological studies assessing whether chronic pain, with minimal or non-inflammatory features, increases the risk of cancer incidence or mortality. The search used Scopus and Web of Science up to 11/03/2025. Quality assessment used the Newcastle–Ottawa Scale. Study characteristics and outcomes were analysed using narrative synthesis, with random-effects meta-analysis and meta-regression conducted where appropriate. A total of 23 studies (12 prospective, 11 retrospective) met the inclusion criteria, of which six were rated as high quality. The outcome data synthesis indicates a small increase in cancer mortality rate ratios, and a potential increase in a subset of organs. A total of three body site-specific analyses suggest that chronic pain may be associated with higher incidence for breast (SIR 2.12–4.8) and prostate (SIR 1.49–5.59) cancers, and with increased mortality for lung cancer (MRR 3.09, 95% CI 1.45–6.62). Ten studies were included for meta-analysis, including four studies rated as high quality. Meta-analysis of hazard ratios showed no association between cancer-related mortality and pain (HR 1.00, 95% CI 0.97–1.04), with consistent estimates across pain subtypes in meta-regression. Our review and meta-analysis do not support an overall association between chronic pain and increased risk of cancer mortality or incidence and highlight multiple methodological and conceptual obstacles to exploring this relationship, including reverse causation and confounding factors such as pain and opioid use association. High-quality studies that rigorously address reverse causation and confounding are warranted.</p>