Grand challenges such as climate change, ageing societies and food security feature prominently on the agenda of policymakers at all scales, from the EU down to local and regional authorities. These are challenges that require the input and collaboration of a diverse set of societal stakeholders to combine different sources of knowledge in new and useful ways - a process that has occupied the minds of economic geographers looking at innovation in recent decades. Work in economic geography has in particular examined infrastructural, capability, network and institutional challenges that may be found in different types of regions. How can these insights improve researchers' and policymakers' understanding of the potential for innovation policies to address grand challenges? In this paper, we review these insights and then identify areas that push economic geographers to go beyond their previous focus and interests, notably by considering innovation policy in light of transformational rather than mere structural failures.