SUMMARY While the past decade has seen an explosion in basic genomic research, the clinical implementation of genomic medicine remains elusive. This Specialized Innovation Program (SIP) will identify and overcome barriers that impede the translational science of rapid genomic medicine discoveries at the point of care by assembling the infrastructure, technology, and strategies to design and develop a rapid genomic diagnostic platform, using the newborn intensive care unit (NICU) as a laboratory. Emerging clinical guidelines support the value and utility of rapid whole-genome sequencing in the NICU, yet multiple barriers impede the widespread use of this technology at the point of care. Specifically, (1) less than half of rare Mendelian diseases are solvable using current sequencing and analytical technologies; (2) industry electronic health record (EHR)-based genomic medicine applications are essentially nonexistent, with a lack of EHR-interfaced platforms that allow for visualization and team-based interpretation of genomic sequencing; (3) translational science strategies to implement genomic medicine into clinical care are currently lacking. To overcome these barriers, the SIP will design and develop an innovative, collaborative, patient-focused, and EHR-interfaced translational platform that efficiently integrates rapid genomic medicine at the point of care, using the NICU as a laboratory. Aim 1 will design novel tools that will improve the discovery of all forms of genetic variation, including difficult-to-detect complex structural variants. These novel tools will be shared as open-source software, with accompanying tools for dissemination and implementation, to empower translational genomic science across the CTSA network. Aim 2 will deploy a portable EHR-interfaced platform for rapid genomic diagnostics that is appropriate, acceptable, and feasible across EHR systems and will catalyze clinical and translational science locally, regionally, and nationally. Aim 3 will use a participatory planning strategy and state of the science dissemination and implementation science methods to develop, tailor, and operationalize strategies to support NICU adoption, implementation, and sustainability of a translational platform for rapid genomic diagnostics. These strategies will be compiled into a generalizable blueprint to foster genomic innovations across the CTSA network and empower broader adoption and sustained implementation of genomic medicine.