Lycopene is a potent lipophilic antioxidant in tomato. We aim to clarify the evidence for associations between tomato and lycopene and multiple health outcomes. Umbrella review of meta-analyses and systematic reviews was performed in humans. A total of 174 articles were searched, 17 articles with 20 health outcomes were identified by eligibility criteria. Tomato intake was inversely associated with all-cause mortality, coronary heart disease mortality, cerebrovascular disease mortality, prostate cancer, and gastric cancer. Dietary lycopene intake or serum lycopene was inversely associated with all-cause mortality, prostate cancer, stroke, cardiovascular disease, metabolic syndrome, and male infertility. Caution was warranted for potential allergy and pollution. The quality of the vast majority of evidence by GRADE was low or very low with the remaining six as moderate. The intake of tomato or lycopene was generally safe and beneficial for multiple health outcomes in humans. But the quality of the evidence was not high.