Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients’ care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy.