The regional and local impact of the COVID-19 crisis is highly heterogeneous, with significant implications for crisis management and policy responses. This paper takes an in-depth look at the territorial impact of the COVID-19 crisis across its different dimensions: health, economic, social and fiscal. It provides a comprehensive overview of national and subnational government response measures to manage the vaccination campaigns across levels of government and mitigate the territorial effects of the crisis. Finally, the paper offers a forward looking perspective on the crisis’ implications for multi-level governance, as well as points for policy-makers to consider as they build more resilient regions.