A general consensus exists among Member States that gaining academic knowledge on its own is not enough for young people to play a role as active citizens and face the socioeconomic realities in their lives, in order to avoid inequity, poverty, discrimination, marginalisation and exclusion. In the 21st century, education needs to go beyond narrow sectoral goals such as academic achievement. In addition, it should contribute actively to the health and well-being of children and young people, whose mental health needs are becoming more evident and demanding. The recent European Commission communication on the achievement of the European Education Area by 2025 (European Commission, 2020) has set in motion a collaborative process to determine how schools can address the learning and socio-emotional needs of their students – in particular, those children who encounter difficulties – and how they can provide students with a balanced, high-quality, education that sets them on a trajectory towards an active, productive and healthy life. This report is in response to such initiatives and to the recognised need for schools across Europe to prioritise and actively promote the mental health and well-being of school children within safe and inclusive contexts. More specifically, it seeks to review the international literature on the promotion of mental health and well-being and the prevention of bullying in schools. In addition, it seeks to develop a theoretical framework to guide the way in which the whole-school system, in collaboration with the community, can be mobilised at various levels to promote mental health and well-being. The report makes recommendations for the effective implementation of a systemic, whole-school approach to the promotion of mental health and well-being and the prevention of bullying in schools across the EU. This report adopts a systemic, whole-school perspective that emphasises the importance of interacting subsystems within and beyond particular individuals and settings.