Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that requires early detection and treatment. Currently, we have three categories of slow-acting disease-modifying antirheumatic drugs (DMARDs): (1) conventional synthetic (csDMARD), (2) biologic (bDMARD), and (3) directed or targeted synthetic (tsDMARD). Objective: This review explores innovative therapeutic modalities for RA, discussing their potential advantages and challenges. The objective is to assess the safety, efficacy, and feasibility of these novel therapies to improve the quality of life for RA patients. Also, focus has been laid on non-pharmacologic modalities in comparison to pharmacologic modalities. Results: This review discusses several innovative therapies for RA, including acrylamide derivatives, coumarin derivatives, JAK1-selective inhibitors, monoclonal antibody adjuvants with methotrexate, the pros, and cons of NRF2 activation as adjunctive therapy, glucocorticoids, bioactive molecules, combination therapy, gene therapy, and other therapies. Each approach presents unique advantages and challenges, reflecting the complexity of RA and the need for personalized treatment strategies. Conclusion: Ongoing research and clinical trials are crucial for assessing the safety, efficacy, and feasibility of these novel therapies. By overcoming the limitations of conventional treatments and tailoring treatment approaches to individual patients, these innovative therapies have the potential to enhance the quality of life for RA patients.