Targeted therapies (TTs), including biologic and targeted synthetic DMARDs, have transformed the management of inflammatory arthritis (IA). However, their use in patients with a history of cancer raises concerns due to the role of immunity in tumor surveillance and the lack of randomized controlled trial data in this population. Recent observational studies and systematic reviews, including over 15,000 patient-years of follow-up, show no increased risk of new or recurrent malignancy with TNF inhibitors compared with csDMARDs. Rituximab appears safe in patients with prior lymphoma, while caution remains warranted for JAK inhibitors and abatacept given potential safety signals observed in other contexts. Importantly, TNF inhibitors initiated within five years of a cancer diagnosis were not associated with higher recurrence risk. The 2024 EULAR Points to Consider provide updated guidance, recommending individualized therapeutic strategies based on cancer type, remission status, and comorbidities, with close collaboration between rheumatologists and oncologists. While current evidence is reassuring for TNF inhibitors, data on other TTs remain limited. Future research should focus on long-term safety, inclusion of broader IA subtypes, and development of personalized cancer risk stratification tools.