Introduction Methotrexate (MTX) is a cornerstone medication in the treatment of autoimmune diseases such as rheumatoid arthritis and psoriasis, as well as various cancers. It is prized for its immunosuppressive and anti-inflammatory properties, and in low doses, is commonly used for long-term disease control in rheumatology. On the other hand, nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed alongside methotrexate to manage inflammation and pain. However, the concurrent use of NSAIDs and methotrexate raises significant concerns regarding drug interactions and potential toxicity. While both are beneficial independently, their combination—especially in certain contexts—can lead to serious, sometimes life-threatening complications. This article explores…