Objective: Physical disorders in patients with severe mental illness (SMI) are common and they tend to be underdiagnosed by clinicians, which might lead to negative treatment outcomes. The presence of substance use disorders could further aggravate the situation. There are existing systematic reviews on physical disorders among individuals with SMI in general but none of these previous reviews stratified their findings by substance use disorder status. This study aimed to synthesize the evidence on the frequency of comorbid physical disorders among patients with SMI with or without substance use disorders. Methods: We searched for studies published in English between 1988 and 2017 in MEDLINE, Embase, CINAHL, PsycINFO, Global Health, Web of Science, Scopus, WHO Global Health Library (Global Index Medicus), Google Scholar, OpenGrey, the Grey Literature Report, Cochrane Library, International Standardized Randomized Controlled Trial Number Registry, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Australian and New Zealand Clinical Trials Registry, and PROSPERO. There was no geographical restriction and the target population was adults (≥18 years) with diagnosed SMI including schizophrenia, bipolar disorder, and other psychotic illnesses. The outcome of interest was physical disorder. Results: A total of 6,994 records were retrieved. Only 30 papers (representing 24 studies) met our inclusion criteria and 13 studies were included in the meta-analysis. The prevalence of most of the reported physical disorders was higher in SMI patients with substance use disorders than in those without substance use disorders. When ranked according to pooled prevalence level, hypertension (35.6%), tardive dyskinesia (35.4%), and hepatitis C (26.9%) were the most prevalent physical disorders among SMI patients with substance use disorders. For SMI patients without substance use disorders, hypertension (32.5%), tardive dyskinesia (25.1%), and endocrine disease (19.0%) were more common. Estimates for diabetes (7.5% vs. 7.5%) and cardiovascular diseases (11.8% vs. 11.3%) were similar across groups. Conclusions: Physical disorders among SMI patients vary by substance use disorder status. Clinicians managing SMI in patients should screen for physical disorders and substance use disorders and provide treatment or referral. Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42017072286.