The academic performance of medical students seems to influence and be influenced by various factors. Identification of the factors that would influence the academic performance may help to modify some of these factors which may be reflecting positively on student’s GPA. Therefore, the objective of present study was to examine the effects of factors such as the student’s demographic data, educational and socio-cultural factors on the academic underachievement of Iranian medical students. In this systematic review study, all the papers related to the investigation of the causes of academic underachievement in case of the Iranian medical students, that were published during the period between 1996 and 2015, were recorded and reviewed. To carry out this purpose, all the Iranian journals and some of the scientific databases such as IranMedex, SID, Magiran, and MedLib, and foreign databases such as PubMed, Web of Science, Google Scholar, ERIC, and Science Direct, were used to search the keywords academic underachievement, medical students, educational status, and education progress. After searching mentioned databases, 218 papers were recorded, 97 of which were unrelated and were omitted during the initial review. After omitting the unrelated papers, 121 papers were reviewed by authors independently, and after the omission of the papers not possessing the criteria to enter the study, 65 papers remained, and finally, after complete reviewing procedure, 10 studies entered the analysis. In conclusion, being married, having second jobs, residing in a dormitory, admission to university by the privilege, low educational level of the parents, long interval between receiving diploma and entering university, male sex, age, not having educational planning and motivation skills, and absence from the classes are the main educational barriers among medical students resulted in underachievement.