Faced with destabilizing conditions in the Anthropocene, infrastructure resilience modeling remains challenged to confront increasingly complex conditions toward quickly and meaningfully advancing adaptation. Data gaps, increasingly interconnected systems, and accurate behavior estimation (across scales and as both gradual and cascading failure) remain challenges for infrastructure modelers. Yet novel approaches are emerging – largely independently – that, if brought together, offer significant opportunities for rapidly advancing how we understand vulnerabilities and surgically invest in resilience. Of particular promise are interdependency modeling, cascading failure modeling, and synthetic network generation. We describe a framework for integrating these three domains toward an integrated modeling framework to estimate infrastructure networks where no data exist, connect infrastructure to establish interdependencies, assess the vulnerabilities of these interconnected infrastructure to hazards, and simulate how failures may propagate across systems. We draw from the literature as an evidence base, provide a conceptual structure for implementation, and conclude by discussing the significance of such a framework and the critical tools it may provide to infrastructure researchers and managers.