Tooth agenesis is the congenital absence of one or more teeth in the normal series due to failures during dental development in the odontogenesis process. Although tooth development mechanisms are more precise in the literature, the etiology of non-syndromic tooth agenesis remains partially unknown. Mutations in genes that regulate the transcription factors involved in tooth development are associated with this condition. Despite advances in genetic research, questions remain about whose understanding might enable more precise and customized treatments. This study aimed to explain the molecular mechanisms associated with non-syndromic tooth agenesis and treatment progression regarding the condition in genetics. The search was non-systematic and performed in MedLine (via PubMed). The inclusion criteria were observational and experimental studies published in English, Portuguese, and Spanish, with open access and without time restrictions. The data analysis was narrative/descriptive. Fifty-three articles were selected. The primary genes associated with non-syndromic tooth agenesis identified in the study include PAX9 and MSX1 – essential for molar and premolar formation; WNT10A and WNT10B – involved in cell signaling during odontogenesis; AXIN2 – related to the regulation of cell control and colorectal cancer risk; EDA and EDAR – crucial for ectodermal structures; and BMP4 – regulates cell differentiation and morphogenesis. These lesions directly affect tooth formation and quantity. Understanding these genetic foundations and the molecular mechanisms of tooth agenesis is essential to improve diagnosis, develop customized therapies, and enhance patients’ quality of life. Continuous research is critical to establish genetic-based therapeutic innovations.