Industrial plants are particularly vulnerable to natural disasters like earthquakes. Seismic events could lead to major hazard accidents in industrial facilities, resulting in both structural and non-structural damages, loss of hazardous substances or disruption of plant’s activities. For that concerning major hazard industrial plants, the European Directive Seveso III emphasises the importance of conducting a safety assessment as part of the risk analysis process. This assessment should pay particular attention to the seismic evaluation of plant components, including tanks, pipelines and their connections. This paper focuses on the seismic vulnerability of pipe-to-tank connections primarily caused by relative displacement between the pipe and the tank’s wall. A comprehensive understanding of these sources of vulnerability is essential for improving safety measures and designing more resilient systems in seismic-prone areas. This study presents the results of an experimental program developed in the framework of the MITPLANT project funded by INAIL (National Institute for Insurance against Accidents at Work). This research aimed at evaluating the seismic behaviour of pipe-to-tank connections under three different loading conditions. The connections were tested under monotonic and reverse cyclic loading to characterise their hysteretic response, failure mechanisms, and key response parameters. The results of the experimental tests will extend the knowledge regarding the dynamic interaction between tanks and pipelines and will provide valuable data to stakeholders and technicians dealing with the performance assessment of complex piping networks in industrial facilities.