Transportation infrastructures are complex systems of various connected components like bridges, roads, tunnels, embankments, retaining walls in case of a highway system or wharfs, cranes, buildings, utility systems in case of port facilities. Due to their spatial extent, they are exposed to variable natural hazards such as earthquakes, tsunami or landslides. Experience from past disastrous events shows that transportation infrastructures are quite vulnerable due to the lack of redundancy, the lengthy repair time, the rerouting difficulties or the cascading failures and interdependencies. Their damage could be greatly disruptive in terms of safety of life, business disruption, access to emergency services and key lifelines utilities, rescue operations and socio-economic impacts. Therefore, in terms of resilience it is important to recognize and quantify the risks and global losses associated to damages of transportation systems and to establish efficient risk mitigation strategies. These include, among others, enhancement of emergency preparedness, strengthening of existing structures and improvement of the recovery planning.Herein an integrated framework for the probabilistic systemic vulnerability and risk assessment of transportation and utility networks is presented, based on the achievements of the recently completed EC project SYNER-G (www.syner-g.eu) and the ongoing EC project STREST (www.strest-eu.org). The infrastructure is modeled according to a detailed taxonomy. The framework encompasses in an integrated fashion all aspects in the chain, from regional hazard to fragility assessment of components to the socio-economic impacts of a natural disaster, accounting for relevant uncertainties within an efficient quantitative simulation scheme, and modeling interactions between multiple component systems in the taxonomy. Selected Performance Indicators (PIs) are calculated for each network based on the estimated damages and functionality losses of the different components under the given hazards.The methodology and tools are demonstrated through case studies in the road network and the harbor of Thessaloniki city, Greece, under seismic hazard and associated geotechnical hazards (i.e. soil liquefaction). The applications include assessments of systems’ performance considering the spatial seismic hazard with correlation of ground motion intensities, the vulnerability of the network components, and the effect of interactions within the system, as well as, between components of different systems. In particular, road disruptions can be caused due to direct damage of road segments and bridges, as well as building and overpass collapses. Harbor operations can be disturbed due to failures of waterfront structures and cargo handling equipment, as well as disruptions to the electric power supply and building collapses. The systemic risk for the road network and harbor is calculated, specifically focusing on the short-term impact of seismic events (just after the earthquake) and the risk curves (i.e. mean annual rates of exceedance for loss in performance of the infrastructures) are provided. The significant elements for the functionality of each system are defined through correlation factors to the system PIs. Such results can contribute to the decision-making regarding the enhancement of existing and the robust development of new infrastructures in the frame of safety and resiliency.