Congenital anomalies encompass a wide range of malformations that could affect various organs and tissues in the newborn and infant population. These disorders that involve defects in or injury to a developing fetus may be a result of genetic abnormalities or mutations, alterations in the intrauterine environment, irregularities in morphogenesis, or chromosomal aberration. The outcome of these defects could lead to minor anomalies or major malformations that are dependent on the complex processes between the prenatal deficit and postnatal environment. Often multiple malformations occur within the same fetus and give rise to a malformation syndrome. Since congenital anomalies are evident at birth, solutions must be found to improve the clinical state and quality of life that a newborn has to lead from infancy through adolescence into adulthood. Transplantation options in this age group are limited due to the shortage of organs and the discrepancy in adult donor size mismatch. Over the past 2 decades tremendous strides have been made in the research of biomaterials, stem cells, organ generation, and tissue engineering to provide viable solutions to a wide range of organ and tissue losses focusing on the adult population. This review intends to highlight the shortage of tissue and organs in neonates and infants with congenital malformations. This is also the first monograph that presents estimation of incidences of the congenital malformations based on an extensive literature search. It also outlines the challenges in clinical management of these entities and presents an organ-based demand for engineered tissues.