BACKGROUND AND AIMS: Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). However, there has not been a detailed evaluation of the characteristics of the published cases of monogenic IBD. Here we systematically review the literature to determine the clinical features, genetic profile, and previously used treatments strategies in monogenic IBD. METHODS: A systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. Seven hundred and fifty individual monogenic IBD cases were identified from 303 eligible articles. RESULTS: The most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA and TTC7A. In total, 63.4% of patients developed IBD before six years of age, 17.4% between ages 10 and 17.9 years, and 10.9% after 18 years of age. There was substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extra-intestinal comorbidity (EIC) before IBD onset but, 76.0% developed at least one EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation (HSCT) were performed in 27.1%, 32.9%, and 23.1% of patients, respectively. CONCLUSION: Monogenic IBD cases while rare have varied extra-intestinal comorbidities and limited treatments options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.