PROJECT SUMMARY/ABSTRACT This is an application for years 21-25 of NIDA's CTN Florida Node Alliance (FNA). The FNA covers Florida, Georgia and Puerto Rico, areas of the US that continue to suffer from high rates of drug overdoses and unceasing opioid, cocaine and methamphetamine epidemics. These areas have unmet treatment needs and experience disparities in the implementation of evidence-based treatments. The FNA aims to build on our record of success in leading and implementing trials in healthcare settings and integrating substance use into mainstream of healthcare. We propose to bring to the CTN the FNA's considerable expertise in adolescent treatment, the HIV and HCV care continua in substance-using populations, mental health comorbidities, e- Health, data science, culturalized science, health economics, training, implementation/dissemination, and work with Hispanic populations. The FNA's research agenda will provide scientific leadership to develop, test, and implement interventions for the full spectrum of substance use in adolescents and adults, and strategies for the integration of SU prevention/screening/treatment services into mainstream adolescent and adult health care. The FNA also aims to apply our expertise in implementation science, data science, and use of electronic health records (EHRs) to promote learning health care systems that build on precision medicine principles by implementing and refining methods to predict individual response to treatment. Building on a foundation of bidirectional collaboration, the FNA proposes to develop, test and implement interventions that address the service delivery continuum in the FNA's clinical and research networks. These networks consist of SUD treatment and general medical settings, health systems, clinical research networks, and practice-based research networks. To achieve its aims, the FNA is proposing an innovative research agenda of concepts that (1) integrate behavioral health and family focused interventions in pediatric care with the use of e-technologies, (2) deliver integrative models of care for comorbid SU and HIV in hospital settings, (3) address the comorbidities of mental health and stimulant use, (4) use EHR, registry and environmental data to improve treatment precision, and (5) use context and culture to improve treatment outcomes. The FNA proposes to collaborate with other Nodes on the design and implementation of CTN trials and by providing the infrastructure and capabilities required for successful study execution. FNA network partners have demonstrated experience in conducting point of care trials and studies that leverage the use of EHR and claims data. The University of Miami CTSI, University of Florida CTSI, and the Georgia CTSA, will bring to the CTN the bioinformatics tools of the CTSA National Consortium. These CTSAs together with partners of the FNA, facilitate access to a diverse patient population of 16+ million patients across a numerous settings such as primary care, EDs, hospitals, FQHCs, school-based clinics, SUD treatment and harm reduction venues.