The presence of karstification processes in the terrain poses a threat to the safety of the foundations of structures, which in the case of gypsum materials becomes more dangerous due to the rate at which they can progress. This work describes the case of a Spanish high-speed bridge whose route runs over a Tertiary gypsum formation belonging to the lower Miocene unit of the Madrid Basin. These are very firm materials in a healthy state, that allow the direct support of shallow foundations, which stand out for their high heterogeneity, with the presence of massive gypsum banks as well as alternating levels of gypsum and clay. However, these materials can be affected by karst processes of dissolution, weathering, and replacement by clays, in which case there is a marked degradation of their mechanical properties, and the eventual local appearance of cavities. In these circumstances, it is necessary to carry out soil improvement treatments, such as compaction grouting, or consider deep foundations with piles that transmit the loads of the structure to a lower substrate in a non-disturbed state. By its nature, the detection of this type of processes by drilling rotary boreholes is not trivial, and there is often uncertainty associated with its spatial variability. This communication presents the results obtained after the execution of a geotechnical research campaign, consisting of the realization of seismic tomography borehole-profiles under each pier and abutment of the bridge, aided by the execution of conventional rotary boreholes. The results of this exploration have made it possible to understand and define the spatial extent of the materials degraded by karstification and the selection of robust foundation typologies that favor the sustainable and resilient nature of the infrastructure.