The article reviews the current state and future prospects of immunotherapy for systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA). It highlights the limitations of conventional treatments like glucocorticoids and immunosuppressants, which often have poor specificity and can lead to tolerance. The article discusses the development and clinical efficacy of novel immunotherapies, such as monoclonal and bispecific antibodies, and CAR-T cell therapy. Monoclonal and bispecific antibodies target various factors involved in disease pathogenesis, including B cells, co-stimulatory molecules, cytokines, and their receptors. CAR-T cell therapy, particularly targeting CD19, has shown promising results in treating SLE and SSc, with recent clinical trials demonstrating significant improvements in patient outcomes. The article also explores the potential of CAR-T cells targeting different cell types, such as cCAR-T, CAAR-T, and CAR-Tregs, to address the complex nature of SADs. Despite the progress, challenges remain, including the need for larger-scale trials to confirm the efficacy and safety of these therapies. The article concludes by emphasizing the potential of immunotherapy to improve patient outcomes and the need for further research to optimize these treatments.The article reviews the current state and future prospects of immunotherapy for systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA). It highlights the limitations of conventional treatments like glucocorticoids and immunosuppressants, which often have poor specificity and can lead to tolerance. The article discusses the development and clinical efficacy of novel immunotherapies, such as monoclonal and bispecific antibodies, and CAR-T cell therapy. Monoclonal and bispecific antibodies target various factors involved in disease pathogenesis, including B cells, co-stimulatory molecules, cytokines, and their receptors. CAR-T cell therapy, particularly targeting CD19, has shown promising results in treating SLE and SSc, with recent clinical trials demonstrating significant improvements in patient outcomes. The article also explores the potential of CAR-T cells targeting different cell types, such as cCAR-T, CAAR-T, and CAR-Tregs, to address the complex nature of SADs. Despite the progress, challenges remain, including the need for larger-scale trials to confirm the efficacy and safety of these therapies. The article concludes by emphasizing the potential of immunotherapy to improve patient outcomes and the need for further research to optimize these treatments.