Abstract Aim: The aim of this study was to evaluate and review articles and researches done on the polymorphism of PAX9 and MSX1 genes in congenitally missing lateral incisors. Materials and methods: A thorough search of the electronic database through Cochrane library, PubMed central, LILACS and BMC and manual hand searching of orthodontic journals was done till March 2020. The keywords included in the search were: “Genetics”, “lateral incisors”, “agenesis”, “PAX9”, “MSX1”. The studies were selected as per the PRISMA guidelines. Articles were shortlisted based on the exclusion and inclusion criterias. Of all the obtained results, 12 studies were selected based on the inclusion criteria and they were analysed for the role of polymorphism of PAX9 and MSX1 genes in the congenitally missing lateral incisors. Results: Results of this systematic study show an association of PAX9, EDA and WNT10A gene pleomorphism with congenitally missing lateral incisors. MSX1 gene however is not shown to have an association with lateral incisor agenesis. Conclusion: This systematic review has provided a clear view on the role of the pleomorphism of different genes on the agenesis of lateral incisors, which will help the reader understand the problem better and handle it with better precision. Future studies are required to further conduct more randomised controlled trials, which will provide more concrete evidence to the claims. Clinical significance: Maxillary lateral incisors are the third most common congenitally missing teeth in the human dentition, preceded only by the third molars and mandibular second premolars The cause of lateral incisor agenesis is thought to be rooted to a genetic etiology.