Regions are embedded in a network of governance with formal and informal competences that determine the scope for regional innovation policy. The multi-level governance of innovation policy has become increasingly complex, thanks to several trends that highlight the role of regions for innovation. This mutual dependence brings to light challenges in multi-level governance that need to be clearly diagnosed to identify adapted governance arrangements and tools for vertical and horizontal co-ordination. Regions also need to engage the right public and private stakeholders, within the region and beyond, to implement their strategies. Adapted monitoring and evaluation tools not only serve these regional strategy needs, they also reveal relevant information for more effective governance co-ordination tools.