Hydrogen will play an important role as an energy carrier to help society decarbonize energy systems. Although storage in salt caverns is a proven concept, hydrogen storage for purposes of power generation, transportation, and industrial use is today an untested concept. This use of hydrogen storage will require the creation of new salt caverns and/or the repurposing of existing ones within salt formations. The magnitude of upscaling will pose important subsurface and engineering challenges associated with intrasalt heterogeneities. In this study, we analyze a three-dimensional seismic reflection survey from the Mississippi Salt Basin and discuss several elements of the basin’s evolution including age of halokinesis and faulting. We relate our observations to subsurface storage in salt domes and present an overview of activity of subsurface energy storage in Mississippi. Our results indicate that the basin experienced three phases of basin evolution during the Early Cretaceous (active halokinesis), the Late Cretaceous (mainly passive basin infilling), and the Cenozoic (passive infilling with minor halokinesis). Fault patterns around salt domes in this region might connect with intrasalt anomalous zones; however, confirmation of this hypothesis requires further investigation including core and petrophysical analysis with improved seismic imaging. Several domes in the Mississippi Salt Basin contain salt caverns storing hydrocarbons. Dome 3, within our study area, experienced several safety issues that ended up with the decommissioning of several caverns. These experiences highlight the importance of characterizing salt domes to optimize salt cavern placement as part of current efforts to upscale subsurface hydrogen storage.