Climate change is increasing the frequency and the intensity of weather events, leading to large-scale disruptions to critical infrastructure systems. The high level of interdependence among these systems further aggravates the extent of disruptions. To mitigate these impacts, models and methods are needed to support rapid decision-making for optimal resource allocation in the aftermath of a disruption and to substantiate investment decisions for the structural reconfiguration of these systems. In this paper, we leverage infrastructure simulation models and Machine Learning (ML) algorithms to develop resilience prediction models. First, we employ an interdependent infrastructure simulation model to generate infrastructure disruption and recovery scenarios and compute the resilience value for each scenario. The infrastructure-, disruption-, and recovery-related attributes are recorded for each scenario and ML algorithms are employed on the synthetic dataset to develop accurate resilience prediction models. The results of the prediction models are analyzed and possible design strategies suggested based on the resilience enhancement attributes. The proposed methodology can support infrastructure agencies in the resource-allocation process for pre- and post-disaster interventions.@en