Osteoarthritis (OA) and rheumatoid arthritis (RA) are among the leading causes of chronic joint pain and disability, resulting in significant healthcare and economic burdens. OA is a degenerative disorder characterized by cartilage degradation, whereas RA is an autoimmune condition that leads to synovial inflammation. Despite their differences, both conditions share similar symptoms such as joint pain, stiffness, and functional decline, which can complicate early diagnosis and delay targeted treatment. Degradation of the extracellular matrix, chondrocyte senescence, and responses to biomechanical stress are considered key molecular events in OA. By contrast, RA is driven by abnormal immune activation, autoantibody production, and ongoing synovial inflammation. This review provides a comparative analysis of OA and RA, focusing on pathophysiology, diagnostic modalities, clinical assessment frameworks, and evolving management strategies. Diagnostic strategies that combine patient evaluation, advanced imaging techniques, and emerging molecular biomarkers to improve early detection are also discussed. Critical evaluations are provided of management strategies that encompass pharmacologic treatments, such as using nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs, biologics, and Janus kinase (JAK) inhibitors, as well as non-pharmacologic interventions, including physical therapy, lifestyle modifications, and surgical options. In addition, the limited disease-modifying options for OA and safety concerns with long-term immunosuppressive therapy in RA are noted, highlighting the need for biomarker guided personalized therapies.