A complex interaction of genetic, environmental, and epigenetic variables leads to congenital impairments, a leading cause of infant morbidity and mortality worldwide. Understanding the molecular causes of congenital diseases has advanced significantly since the development of genomic medicine. This entry examines how developments have transformed diagnosis, prevention, and treatment methods. This entry also examines the genetic and epigenetic causes of significant congenital diseases such as Turner syndrome, Down syndrome, cleft lip and palate, neural tube defects, and congenital heart defects. Prenatal and neonatal genomic screening, the function of gene-environment interactions, and the moral ramifications of new genomic technologies are also highlighted in this entry. The entry highlights the revolutionary potential of genomes in diagnosing, treating, and maybe preventing congenital disorders by fusing state-of-the-art research with practical applications.