Missions have been widely discussed as potential solutions to the grand challenges associated with social, economic and environmental issues. This represents a promising agenda for the state and its role in setting and managing missions, but discussions to date have not always reflected the multipolarity of many regional settings, nor the challenges of implementing policies within localised settings. In our paper we explore how missions may be recast as sub-national endeavours, benefiting from trial and test place-based experiments, localised knowledge, lower set up costs and partnership working arrangements among partners who know each other. We illustrate our ideas through three linked initiatives taking place in Wales. The Cardiff Capital Region (CCR) Challenge Fund, the Innovative Future Services project (Infuse) and challenge led policy action. We conclude by reviewing the role of the university in providing a safe space for such experiments.