<p>While biologics have proven to be effective in treating immune-mediated inflammatory diseases (IMIDs), the label of most biologics carries a warning regarding their use in patients with active cancer or a history of cancer. Consequently, there has been a reluctance to prescribe these medications to patients with a history of cancer, and little is known about the risk of new and/or recurrent cancer in patients with IMIDs treated with biologics and a previous cancer. This systematic review and meta-analysis searched PubMed, Embase, Cochrane Library, and Web of Science up to February 23, 2024, for studies on the risk of new and/or recurrent cancer following treatment with biologics in patients with IMIDs and a previous cancer compared to controls (PROSPERO; CRD42024516899). Controls included patients receiving non-biological or no therapy. Risk estimates were calculated with random-effects meta-analysis with I² statistics to estimate between-study heterogeneity. In total, 20 articles comprising 4736 patients treated with biologics with 15,646 patient-years of follow-up were included. Treatment with tumor necrosis factor (TNF)-α inhibitors (TNFi), interleukin (IL)-12/23 inhibitors or vedolizumab did not appear to lead to increased risk of new or recurrent cancer in patients with IMIDs and a previous cancer compared to conventional systemics or no therapy. The results are reassuring to patients and physicians prescribing biologics to patients with IMIDs. However, further studies are needed especially on newer biologics and decision on initiation of biologics in patients with cancers should be based on an individual assessment.</p>