Exfoliative toxins of Staphylococcus aureus have been associated with Staphylococcal scalded-skin syndrome (SSSS) and bullous impetigo. Despite many reports on the exfoliative toxin-producing S. aureus in Iran over the past years, a comprehensive analysis of these studies are still rare endeavors. This systematic review aimed to determine the overall prevalence of exfoliative toxin genes (i.e. eta, etb, and etd) among S. aureus isolated from patients in Iran. An electronic search was conducted in the MEDLINE/PubMed, Scopus, and Google scholar databases for all documents published from 1 January 2010 through 1 December 2018. Of the 735 records identified from the databases, 14 studies fulfilled the eligibility criteria. The overall prevalence of eta, etb, and etd genes among S. aureus strains were 13.057% (95% CI: 2.930–28.885%), 3.601% (95% CI: 0.901–8.002%), and 21.922% (95% CI: 3.012–83.237%), respectively. The most prevalent genotypes of eta-positive S. aureus in Iran were staphylococcal cassette chromosome mec (SCCmec) type IV, accessory gene regulator (agr) group I, S. aureus Protein A (spa) type t021, and sequence type 30 (ST30). Regarding etb, the most common genotypes were SCCmec III, spa t005, and ST22. In conclusion, the prevalence of S. aureus strains harboring exfoliative toxin genes varies throughout Iran and that these strains, especially those carrying eta, might be more prevalent in some Iranian provinces, such as Mazandaran and Zanjan. Further researches are encouraged to understand the transmission, burden, and risk factors associated with infections caused by exfoliative toxin-producing S. aureus.