Advancing from phenomenological, evidence-based, person-centered, and personalized care, health and social care systems currently undergo a transformation towards personalized, preventive, predictive, participative precision medicine (5PM), supported by technology. It considers individual health status, conditions, genetic and genomic dispositions in personal social, occupational, environmental and behavioral context, understanding the pathology of diseases and turning health and social care from reactive to proactive. Thereby, we have to enable communication and cooperation between all actors from different knowledge spaces, representing different disciplines, using different methodologies, perspectives, intentions, languages, etc. Therefore, the knowledge-based, multidisciplinary, highly complex and dynamic 5PM ecosystem must be consistently and formally represented. Beside their opportunities, the deployed advanced technologies also bear risks to be managed. Beside the relationships between technology and human actors, the behavior of intelligent and autonomous systems must be considered from a humanistic, moral and ethical perspective. The outcome is a system-theoretical, architecture-centric, ontology-based, policy-driven approach for designing and managing intelligent and sustainable 5PM ecosystems. Developed by the author over the last 30 years. The related model and framework has been meanwhile standardized as the ISO 23903 Interoperability and Integration Reference Architecture, defined as mandatory for any specification or project at ISO, CEN, IEEE, OMG, etc., addressing more than one domain. Thereby, it manages also security, privacy and trust in detail. The Keynote introduces necessary standards and methodologies for designing and managing 5P medicine ecosystems as well as practical examples.