In the context of the preparation of the future research and innovation Framework Programme of the European Union (FP9), the study collects and analyses evidence of current and recent mission-oriented research and innovation initiatives in European Member States and other major economies around the world. The study includes a desk research improving the understanding of mission-oriented R&I initiatives, a definition, and an inventory and analysis of over forty ongoing initiatives (of which seven in depth cases) addressing major global challenges, such as climate change, health, ageing or food security. The analyses explore implementation and management, including their governance structure, the policy mix as well as the monitoring systems and evaluation mechanisms. The Study highlights that there is a plurality of mission-oriented R&I initiatives. Directionality and intentionality nevertheless differentiate them from other initiatives, such as those that are challenge-driven. The success of these initiatives highly depends on pre-conditions, such as institutions and policies already in place as well as existing capacities and knowledge.