This umbrella review evaluates the relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and cancer incidence, focusing on the overall association with multiple cancer types. The review includes 80 meta-analyses covering 20 unique cancer outcomes. Key findings indicate that NSAIDs may reduce the risk of several cancers, including breast, central nervous system (CNS), esophageal, gastric, head and neck, hepatocellular, colorectal, endometrial, lung, ovary, prostate, and pancreatic cancers. However, regular intake of any dose of non-aspirin NSAIDs (NA-NSAIDs) may increase the incidence of kidney cancer. The review also highlights the potential side effects of NSAIDs, such as hemorrhage, digestive symptoms, and peptic ulcer, which limit their use for cancer prevention. Most included studies are rated as low quality due to methodological issues, and the dose-response relationship between NSAID intake and cancer risk remains inconsistent. The review concludes that while NSAIDs show promise in reducing cancer incidence, more high-quality prospective studies are needed to confirm these findings and address limitations in the current evidence.This umbrella review evaluates the relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and cancer incidence, focusing on the overall association with multiple cancer types. The review includes 80 meta-analyses covering 20 unique cancer outcomes. Key findings indicate that NSAIDs may reduce the risk of several cancers, including breast, central nervous system (CNS), esophageal, gastric, head and neck, hepatocellular, colorectal, endometrial, lung, ovary, prostate, and pancreatic cancers. However, regular intake of any dose of non-aspirin NSAIDs (NA-NSAIDs) may increase the incidence of kidney cancer. The review also highlights the potential side effects of NSAIDs, such as hemorrhage, digestive symptoms, and peptic ulcer, which limit their use for cancer prevention. Most included studies are rated as low quality due to methodological issues, and the dose-response relationship between NSAID intake and cancer risk remains inconsistent. The review concludes that while NSAIDs show promise in reducing cancer incidence, more high-quality prospective studies are needed to confirm these findings and address limitations in the current evidence.