Natural events such as earthquakes and floods in past years caused major disasters in industrial areas. Past disasters prompted public administrations to introduce specific directives (e.g., Seveso III), aimed at establishing risk assessment procedures, including seismic vulnerability analysis of critical mechanical components. Seismic damage to structural and non-structural elements in major hazard industrial plants represents a serious threat. These elements often include large-capacity storage tanks connected to complex piping networks, valves, and process units. Among the various components, the interface between storage tanks and connected piping systems represents a particularly vulnerable zone where relative displacements and stress concentrations can lead to mechanical failure during earthquakes. Unlike conventional structural elements, these connections are subject to multi-directional loads and dynamic interactions that are highly sensitive to geometric, material, and layout conditions. Seismic damage at these junctions can result in the release of hazardous substances, with cascading effects on plant safety and emergency response capabilities. Therefore, understanding and quantifying the seismic behaviour of tank-to-pipe connections is essential for the development of resilient storage systems. This study aims to investigate the seismic vulnerability of pipe-to-tank connections through an integrated approach combining numerical modelling and experimental testing in the framework of the MITPLANT project funded by the National Institute for Insurance against Accidents at Work. Experimental monotonic and cyclic tests were performed to investigate the dynamic response of typical unreinforced connection configurations under two different loading conditions. After that, experimental-based finite element models were developed to investigate the performance of different piping layout configurations.