Using examples from the COVID-19 pandemic, this paper reviews the contribution a City Region Food Systems (CRFS) approach makes to regional sustainability and resilience for existing and future shocks including climate change. We include both explicit interventions under United Nations Food and Agriculture Organization (FAO-RUAF) led initiatives, as well as ad hoc efforts that engage with elements of the CRFS approach. To provide context, we begin with a literature review of the CRFS approach followed by an overview of the global food crisis, where we outline many of the challenges inherent to the industrial capital driven food system. Next, we elaborate three key entry points for the CRFS approach—multistakeholder engagement across urban rural spaces; the infrastructure needed to support more robust CRFS; system centered planning, and, the role of policy in enabling (or thwarting) food system sustainability. The pandemic raises questions and provides insights about how to foster more resilient food systems, and provides lessons for the future for the City Region Food System approach in the context of others shocks including climate change.