Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by periodic flare-ups and remissions, causing multi-organ damage. It is marked by the production of autoantibodies that lead to inflammation and tissue injury. While advances have been made in understanding SLE's pathogenesis, treatments continue to rely on broad immunosuppressive therapies, with more targeted therapies emerging as promising options. This review explores the mechanisms behind SLE and evaluates current and future therapeutic strategies. Aim: This review aims to provide an updated overview of the pathogenesis of SLE, recent advances in diagnostic approaches, and the development of targeted treatments, focusing on the potential for personalized therapy. Methods: The review synthesizes recent literature on SLE epidemiology, pathogenesis, diagnostic criteria, and therapeutic advancements. It explores the roles of adaptive and innate immunity, mitochondrial dysfunction, apoptosis, and interferon involvement in disease progression. Results: SLE's pathogenesis involves dysregulated immune responses, with significant contributions from B and T lymphocytes, type-I interferon (IFN) production, neutrophil dysfunction, and mitochondrial abnormalities. Advances in diagnostic tools, including anti-dsDNA and anti-ENA antibodies, have improved disease identification.