Health policy challenges, such as the increase in chronic diseases, require the transformation of the fragmented and acute care-oriented healthcare system into a collaborative, coordinated system to improve population health. As health is a result of many determinants, healthcare cannot bring about better health without partnering with services outside the medical sector to address the various determinants. Such comprehensive health approaches must understand and address the complex needs of all groups in the population and require new care models to strengthen primary healthcare and clinical-community partnerships. As new care models are difficult to implement in daily practice, there is a need to know how to support and facilitate those practice and system-wide changes. To date, there is a lack of such application-oriented implementation research in Switzerland. The aim of this thesis was therefore to fill some of these gaps by conducting three studies. Study A analyzed the concept of Learning Collaboratives to implement new primary care models and developed a common framework for Patient Medical Home transformation within Academic Health Centers (AHCs). Results show that Learning Collaboratives support change and lead to important changes in culture, such as improvement in orientation and interprofessional collaboration. Study B analyzed how clinical-community partnerships are organized and developed six key building blocks for successful partnerships. Study C analyzed the health of female sex workers and showed, based on the significantly higher rates of mental disorders and unmet psychosocial needs compared with the general population, the importance of intersectoral collaboration and care.