Tooth agenesis is one of the most common developmental abnormalities of the human dentition and may occur as an isolated finding or as part of a syndromic condition. Although environmental factors can interfere with odontogenesis, genetic alterations affecting epithelial–mesenchymal signalling represent major determinants of congenital tooth absence. This narrative review summarizes the principal genes and molecular pathways involved in tooth agenesis and discusses their potential relevance for diagnosis, genetic counselling, and multidisciplinary dental management. A focused literature review was performed using PubMed, with emphasis on studies addressing the genetic basis of non-syndromic and syndromic tooth agenesis, genotype–phenotype relationships, and clinical implications. Particular attention was given to PAX9, MSX1, WNT10A, AXIN2, EDA, and LRP6. Tooth development depends on tightly regulated interactions between the oral epithelium and neural crest-derived mesenchyme. Alterations involving WNT/β-catenin, BMP, FGF, SHH, and EDA/NF-κB signalling can interrupt odontogenesis. PAX9 and MSX1 variants are classically associated with non-syndromic tooth agenesis, whereas WNT10A has emerged as an important contributor to both isolated and syndromic forms. AXIN2 is of particular clinical interest because pathogenic variants have been described in families presenting both severe tooth agenesis and colorectal neoplasia. The distribution and severity of missing teeth may therefore provide information relevant to the underlying genetic defect. Tooth agenesis should increasingly be regarded as a developmental phenotype with heterogeneous molecular causes rather than solely as a localized dental anomaly. Recognition of characteristic phenotypes and appropriate referral for genetic evaluation in selected patients may improve diagnosis, counselling, and individualized long-term treatment planning.