Objective To evaluate systemic exposures associated with molar incisor hypomineralization (MIH). Methods This systematic review was performed using published observational studies that evaluated the systemic exposures associated with MIH. The sources of articles searched were PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library and Grey literature. The risk of bias was analysed according to the Newcastle‐Ottawa Scale for quality assessment. The meta‐analysis was performed considering the exposures during the prenatal, perinatal and postnatal periods using the CMA software. Results A total of 4207 articles were identified. Twenty‐nine studies were eligible for inclusion and 27 were included in the meta‐analysis. The studies presented low and moderate risks of bias, except for one that was classified as having a high risk of bias. Maternal illness during pregnancy (OR 1.40; 95% CI 1.18‐1.65, P < 0.0001) and psychological stress (OR = 2.65; 95% CI 1.52‐4.63; P = 0.001) was observed to be significantly associated with higher odds of MIH. During the perinatal period, caesarean delivery (OR = 1.32, 95% CI 1.11‐1.57, P = 0.001) and delivery complications (OR = 2.06; 95% CI 1.47‐2.88, P < 0.0001) were also associated with MIH. In the postnatal period, only respiratory diseases (OR = 1.98; 95% CI 1.45‐2.70, P < 0.0001) and fever (OR = 1.50; 95% CI 1.22‐1.84; P < 0.0001) were associated with higher prevalence of MIH. The evidence was graded as very low quality. Conclusions Maternal illness, psychological stress, caesarean delivery, delivery complications, respiratory diseases and fever during the first years of a child's life were significantly associated with a higher odds of MIH. However, this should be interpreted with caution, once the primary studies were observational, with serious limitations according to the risk of bias, imprecision, and inconsistency. Further, well‐designed cohort studies are still required.