: Inflammatory arthritides includes a range of joint disorders, such as osteoarthritis and rheumatoid arthritis, as well as inflammatory conditions like gout and lupus. This review investigates the pathophysiology, therapeutic challenges, and evolving treatment landscape of arthritis, with a particular focus on the clinical roles of rituximab, apremilast, and upadacitinib. : A comprehensive analysis was undertaken to evaluate the current clinical application, therapeutic efficacy, and safety profiles of selected biosimilar and targeted synthetic disease-modifying antirheumatic drugs (bsDMARDs and tsDMARDs). This overview placed particular emphasis on three key agents-rituximab, apremilast, and upadacitinib-each exemplifying distinct immunomodulatory mechanisms. By focusing on these agents, the analysis highlights the evolving landscape of targeted therapies in rheumatology and underscores the importance of personalized treatment selection based on the disease phenotype, prior therapeutic responses, and comorbid conditions. : Rituximab, apremilast, and upadacitinib each present valuable therapeutic options for patients who have shown inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or nonsteroidal anti-inflammatory drugs (NSAIDs). : Despite the complexity and heterogeneity of arthritis, agents like rituximab, apremilast, and upadacitinib have expanded the therapeutic possibilities in treating this disease and improved its management. Continued research is essential to optimize patient-specific treatment strategies and explore novel molecular targets.