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Abstract This paper proposes a novel simulation‐based hybrid approach coupled with time‐dependent Bayesian network analysis to model multi‐infrastructure vulnerability over time under physical, spatial, and informational uncertainties while considering cascading failures within and across infrastructure networks. Unlike existing studies that unrealistically assume that infrastructure managers have full knowledge of all the infrastructure systems, the proposed approach considers a realistic scenario where complete information about the infrastructure network topology or the supply–demand flow characteristics is not available while estimating multi‐infrastructure vulnerability. A novel heuristic algorithm is proposed to construct a dynamic fault tree to abstract the network topology of any infrastructure. In addition, to account for the unavailability of exact supply–demand flow characteristics, the proposed approach constructs the interdependence links across infrastructure network systems using different simulated parameters considering the physical, logical, and geographical dependencies. Finally, using parameters for geographical proximity, infrastructure managers' risk perception, and the relative importance of one infrastructure on another, the multi‐infrastructure vulnerability over time is estimated. Results from the numerical experiment show that for an opportunistic risk perception, the interdependencies attribute to redundancies, and with an increase in redundancy, the vulnerability decreases. On the other hand, from a conservative risk perspective, the interdependencies attribute to deficiencies/liabilities, and the vulnerability increases with an increase in the number of such interdependencies.