Aim of the Study: This review aims to systematically synthesize the body of literature examining the association between neighborhood socioeconomic disadvantage and serious mental illness (SMI)–type 2 diabetes (T2D) co-occurrence. Methods: We conducted an electronic search of four databases: PubMed, Scopus, Medline, and Web of Science. Studies were considered eligible if they were published in English, peer reviewed, quantitative, and focused on the association between neighborhood disadvantage and SMI-T2D comorbidity. Study conduct and reporting complied with PRISMA guidelines, and the protocol is made available at PROSPERO (CRD42017083483). Results: The one eligible study identified reported a higher burden of T2D in persons with SMI but provided only a tentative support for the association between neighborhood disadvantage and SMI-T2D co-occurrence. Conclusion: Research into neighborhood effects on SMI-T2D comorbidity is still in its infancy and the available evidence inconclusive. This points to an urgent need for attention to the knowledge gap in this important area of public health. Further research is needed to understand the health resource implications of the association between neighborhood deprivation and SMI-T2D comorbidity and the casual pathways linking them.