Systemic lupus erythematosus (SLE) is a multisystem, multifocal, chronic autoimmune disease that involves systemic inflammation and is mediated by rogue immune responses. Traditional medicines such as corticosteroids and immunosuppressants are associated with serious systemic adverse reactions and lack specificity to the disease. The recent developments in targeted drug delivery systems offer a revolutionary method of SLE treatment with enhanced treatment accuracy and reduced off-target toxicity. This chapter discusses the present and the prospective of targeted delivery systems, including nanoparticles, liposomes, micelles, and antibody-drug conjugates, that can deliver therapeutic agents specifically to inflamed tissues or immune cells or to specific molecular targets involved in the pathogenesis of SLE. The chapter explores the design, targeting mechanisms (i.e., ligand-receptor interactions and pH-sensitive release), and preclinical and clinical development of such systems. Issues with clinical translation and the opportunities of its application to individual treatment regimens are also addressed.