Molar incisor hypomineralization (MIH) is a defect of the dental enamel that predominantly affects first molars and permanent incisors. Identifying the significant risk factors associated with MIH occurrence is essential for the implementation of prevention strategies. The purpose of this systematic review was to determine the etiological factors associated with MIH. A literature search was carried out from six databases until 2022; it covered pre-, peri-, and postnatal etiological factors. The PECOS strategy, PRISMA criteria, and the Newcastle–Ottawa scale were used, and 40 publications were selected for qualitative analysis as well as 25 for meta-analysis. Our results revealed an association between a history of illness during pregnancy (OR 4.03 (95% CI, 1.33–12.16),p= 0.01) and low weight at birth (OR 1.23 (95% CI, 1.10–1.38),p= 0.0005). Furthermore, general illness in childhood (OR 4.06 (95% CI, 2.03–8.11),p= 0.0001), antibiotic use (OR 1.76 (95% CI, 1.31–2.37),p= 0.0002), and high fever during early childhood (OR 1.48 (95% CI, 1.18–1.84),p= 0.0005) were associated with MIH. In conclusion, the etiology of MIH was found to be multifactorial. Children with health disorders in the first years of life and those whose mothers underwent illnesses during pregnancy might be more susceptible to MIH.