Underlying genetic disorders should be considered when conducting a postmortem investigation following sudden, unexpected death in infancy. Rare genetic conditions, particularly those affecting the cardiac and neurologic systems, may predispose neonates and infants to sudden death. Due to nonspecific or absent physical features associated with these conditions, as well as a young age at death, these genetic conditions may not have been appreciated during the infant’s lifetime. With current advances in genomic technology, exome sequencing (ES) or genome sequencing (GS) facilitates a comprehensive evaluation that may identify these genetic diagnoses, recognizing that appropriate genetic counseling is warranted and logistical barriers may make ES or GS difficult to access. Nonetheless, awareness of these diagnostic approaches and their potential yield is crucial for clinicians caring for families who have experienced the sudden and unexpected loss of a child.