Transformation is a complex yet critical process to meet new challenges and rising demands in health systems. Across the European Union, countries are grappling with the rising costs of health care and workforce shortages, while dealing with health service backlogs in the aftermath of the COVID-19 pandemic and the increasingly evident consequences of climate change. Many health systems are struggling to adapt and embrace the adjustment or change required to tackle these issues. This highlights the importance of strengthening health systems resilience and effectiveness through transformation. From technological progress to implementing systemic and organizational changes, transformation can encompass the implementation of different types of innovations. It is a process which requires dedicated resources, long-term investment, intersectoral and political commitment, as well as an overall supportive environment. Although the organization and delivery of health care and health systems more broadly is primarily the responsibility of the EU Member States, there are different ways in which the EU can support and facilitate transformation.