We performed a systematic review and meta-analysis of evidence for prevention of future cancers following metabolic bariatric surgery (MBS). MBS was associated with significantly reduced overall cancer incidence (RR 0.62, 95% CI 0.46–0.84, p < 0.002), obesity-related cancer (RR 0.59, 95% CI 0.39–0.90, p = 0.01) and cancer-associated mortality (RR 0.51, 95% CI 0.42–0.62, p < 0.00001). In specific cancers, bariatric surgery was associated with reduction in future incidence of hepatocellular carcinoma (RR 0.35, 95% CI 0.22–0.55, p < 0.00001), colorectal cancer (RR 0.63, CI 0.50–0.81, p = 0.0002), pancreatic cancer (RR 0.52, 95% CI 0.29–0.93, p = 0.03) and gallbladder cancer (RR 0.41, 95% CI 0.18–0.96, p = 0.04), as well as female specific cancers, including breast cancer (RR 0.56, 95% CI 0.44–0.71, p < 0.00001), endometrial cancer (RR 0.38, 95% CI 0.26–0.55, p < 0.00001) and ovarian cancer (RR 0.45, 95% CI 0.31–0.64, p < 0.0001). Obesity-associated carcinogenesis is related to metabolic syndrome; visceral adipose dysfunction; aromatase activity and detrimental cytokine, adipokine and exosomal miRNA release. MBS improves metabolic syndrome, results in long-term weight loss in morbidly obese patients, and may decrease future overall cancer incidence and mortality.