Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hypotheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferatoractivated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.