<p>Assessing network vulnerability is fundamental to several planning and management activities aimed at building resilient-by-design transport systems. The transport research community has made significant progress in this direction. However, existing contributions mostly focus on identifying critical components, assessing socioeconomic impacts of recorded or hypothetical incidents, and/or evaluating vulnerability against specific types of hazards. Drawing on a concise yet systematic literature review, this paper introduces a comprehensive analytical framework for evaluating the system-level vulnerability of road networks, accounting simultaneously for a range of potential stressors. The framework employs a bi-modular structure to reproduce distinct disruption scenarios and network dismantling strategies, integrating transport modeling, graph-theoretic, heuristic, and statistical techniques. It is applied to case studies involving networks of different topology, demand structure, and scale, as well as varying modelling parameters and ethical principles. Experimental results demonstrate the heterogeneous response of road networks to different disruption types and intensities and the framework’s ability to sufficiently account for interactions between demand, capacity, topology, and disruption dynamics. Moreover, the framework appears sensitive enough to the adopted transport modeling and impact aggregation principles. It therefore allows planners and decision-makers to assess vulnerability with flexibility to different goals and contexts. Findings also indicate that infrastructure upgrades lacking a balance between efficiency gains and enablers of network robustness, such as stable path redundancy, may not alleviate network vulnerability effectively. Finally, they reveal that assessing vulnerability by solely relying on pessimistic assumptions may bias analytical outcomes and decision-making. The paper concludes with insights into infrastructure planning and future research.</p>