<p>The co-occurrence of axial spondyloarthritis (SpA) and rheumatoid arthritis (RA) is rarely reported and poses significant diagnostic and therapeutic challenges due to their distinct pathophysiological mechanisms. While tumor necrosis factor (TNF) inhibitors are effective for both conditions, optimal strategies for patients with inadequate response remain unclear. We report a 65-year-old male with a long-standing history of HLA-B27–positive ankylosing spondylitis (AS) with radiographic bamboo spine who subsequently developed seropositive RA. After 15 years of successful treatment with adalimumab, the patient developed peroneal tendonitis suggestive of active enthesitis, prompting a switch to bimekizumab, an IL-17&#xa0;A/F inhibitor. Although the tendonitis improved, the patient experienced a severe flare of peripheral polyarthritis within one year. Switching to a Janus kinase (JAK) inhibitor led to rapid improvement of both RA-related arthritis and AS manifestations. Our literature review identified a limited number of reported SpA–RA overlap cases treated with biologics or JAK inhibitors (<i>n</i> = 6). Together with our case, all patients had a history of treatment with TNF inhibitors. Among them, three achieved successful therapeutic responses, whereas the remaining four experienced primary or secondary treatment failure, respectively. Our case, together with one prior report, suggests that IL-17 inhibitors may be effective for SpA-related manifestations but insufficient for controlling RA-associated synovitis, even in cases of SpA–RA overlap. Although the number of reported cases remains limited, this case-based review suggests the different patterns of therapeutic response consistent with known differences in inflammatory pathways in SpA–RA overlap and underscores the importance of individualized therapeutic strategies integrating clinical phenotype and treatment response.</p>