The increasing trend towards the global use of Information Technology (IT) is currently determining the need for more and better infrastructures (both physical and digital) for processing, storing and transferring large amounts of data. As Critical Infrastructure (CI) that is potentially exposed and vulnerable to the impact of different types of phenomena (natural, technological, na-tech, etc.), data centers have to guarantee higher levels of security (physical, logical and operational), reliability and efficiency in the provision of services. Starting from a discussion of the main evidence related to this topic, considering both the most recent cases of failure and serious damage to data centers and the evolution of international and European regulation and standards, the authors propose an analytical methodology to assess the territorial risk factors for data centers by a multirisk, multi-dimensional and systemic approach. This proposal leads not only to a more explicit definition of exposure and vulnerable components, but also to the recognition of resources that—in the case of accidental events involving (directly or indirectly) data center infrastructures—may be implemented at different territorial levels as “protection” factors to ensure business continuity by considering the entire resilience cycle, from the prevention phase to the response and recovery phases.