Cities and their agglomerations are home to a large number of critical infrastructures that provide essential services in a geographically-narrow space. Because the critical infrastructures in a city are physically and logically dependent on each another, an incident in one infrastructure can have impacts on the entire city and its population. Thus, detailed risk analyses that strongly focus on the interactions within and between infrastructures, and on the potential cascading effects on the population are vital to protecting the critical supply infrastructures.This chapter proposes a general cross-domain simulation framework that describes the major critical infrastructure networks in a large city at appropriate levels of abstraction. Unlike current approaches, the proposed framework focuses on the dynamic relationships between the networks and integrates stochastic models to achieve a realistic representation. The framework supports detailed assessments of the effects of threats on individual critical infrastructures and the potential cascading effects in the network of critical infrastructures.