Immune-mediated inflammatory diseases (IMIDs) represent a heterogeneous group of disorders characterized by chronic inflammation. Their long disease duration and relapsing nature often necessitate long-term, sometimes lifelong, pharmacotherapy. However, the adverse effects associated with these medications cannot be overlooked, with particular attention warranted for the potential risk of malignancy. This article reviews the current evidence regarding the oncogenic risk of major therapeutic agents used for IMIDs, aiming to enhance clinicians' comprehensive understanding of these drugs. For IMIDs patients with a history of malignancy or those possessing other risk factors for cancer, this knowledge may encourage more deliberate deliberation and a more thorough assessment when selecting appropriate treatment options, thereby facilitating better management of drug-associated malignancy risks.