Inflammation is critical to the formation and development of tumors and is closely associated with cancer. Therefore, addressing inflammation and the mediators that contribute to the inflammatory process may be a useful strategy for both cancer prevention and treatment. Tumor predisposition can be attributed to inflammation. It has been demonstrated that NSAIDs can modify the tumor microenvironment by enhancing apoptosis and chemosensitivity and reducing cell migration. There has been a recent rise in interest in drug repositioning or repurposing because the development of innovative medications is expensive, timeconsuming, and presents a considerable obstacle to drug discovery. Repurposing drugs is crucial for the quicker and less expensive development of anticancer medicines, according to an increasing amount of research. This review summarizes the antiproliferative activity of derivatives of NSAIDs such as Diclofenac, Etodolac, Celecoxib, Ibuprofen, Tolmetin, and Sulindac, published between 2017 and 2023. Their mechanism of action and structural activity relationships (SARs) were also discussed to set the path for potential future repositioning of NSAIDs for clinical deployment in the treatment of cancer.