Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by heterogeneous clinical manifestations and diverse autoantibody production. Despite advances in treatment, many patients experience disease flares throughout their lives, and current biomarkers like anti-double-stranded DNA antibodies and serum complement levels have limitations in accurately reflecting disease activity. This review examines emerging and established biomarkers for SLE diagnosis, disease activity monitoring, and treatment response prediction. We discuss immune cell subsets as potential biomarkers, focusing on plasmacytoid dendritic cells, T cell and B cell subsets, especially focused on T cell subsets. The review highlights how imbalances in these cellular populations correlate with disease activity and specific organ involvement. Furthermore, we discuss cytokines, chemokines, autoantibodies, and complement as biomarkers in SLE. The identification and validation of reliable biomarkers in SLE will ultimately improve clinical decision-making regarding treatment selection, glucocorticoid tapering, and prediction of disease remission, leading to more personalized and effective management strategies.