For improving quality, safety and efficiency of care processes, health care systems perform two paradigm changes: the organizational transformation of the health care system from organization-centric to person-centric structures and the methodological transformation from the traditional phenomenological approach to individualized health care based on translational medicine. Both paradigm changes are interrelated and require advanced interoperability between different organizations and multiple disciplines. The paper presents a system-theoretical, architecture-centric approach to analyze, design and develop the systems of health care and medicine for enabling personalized health services. According to the translational medicine paradigm, the considered model must be able to describe the subject of care at all levels of granularity from elements to population including the technologies applied at those levels to perform diagnosis and therapy. The system components reflected through different domains, their concepts and interrelations must be consistently described based on the domain ontologies representing those system perspectives. The medical and technological instances of the personalized health system are exemplified, thereby especially focusing on nano and micro levels and discussing biological and technical sensors and actuators, but also addressing profiling, bridging between genotyping and phenotyping and thereby combining molecular and epidemiological studies.