Critical infrastructure forms the backbone of modern society, with multiple connected systems such as power, water, and transportation supporting the day-to-day functioning of communities and wider regions. These systems are not only physically dependent on one another, but rely on cyber and social dependencies, as well. Moreover, management of critical infrastructure is the responsibility of multiple public and private entities. Thus, while there is a growing need to strengthen infrastructure resilience to disruption, assessing and implementing resilience across complex interdependencies remains a challenge. This chapter, therefore, presents a methodology for cyber-resilience assessment (CRA) at a regional scale, describing a wide range of potential analytical and modeling techniques that target this issue. This culminates in a case study of the Department of Homeland Security’s (DHS) Regional Resilience Assessment Program (RRAP) CRA of the Ashburn, Virginia, which contains a high concentration of critical data centers. Such CRA approaches can be easily adapted for any region of interest, allowing for collaboration among diverse stakeholders and the identification of improvements that strengthen regional cyber and physical resilience.