Enterobacteriaceae is present in various niches worldwide (i.e., the gastrointestinal tracts of animals, clinical specimens, and diverse environments) and hosts some well-known pathogens (i.e., salmonellas, shigellas and pathogenic coliforms). No investigation has focused on its occurrence in marine salterns, and it is not clear if these hypersaline environments could be a reservoir for these bacteria including some potentially harmful members. In this study, a two-year metabarcoding survey was carried out on samples collected from different ponds of the “Saline di Tarquinia” salterns and the nearby coastal waters. Enterobacteriaceae was recorded almost constantly in the seawaters feeding the saltern. Its abundance was generally higher in the sea than in the ponds, probably due to the higher anthropic impact. The same trend was evidenced for the key genus (Escherichia/Shigella) and OTU (OTU 5) of the Enterobacteriaceae community. Various parameters affected taxon/OTU abundance: Enterobacteriaceae, Escherichia/Shigella and OTU5 decreased with increasing salinity and rains; moreover, Escherichia/Shigella and OTU 5 were higher in autumn than in spring. Although Enterobacteriaceae did not seem to find the most favourable conditions for a high-abundance persistence in the saltern environment, it did not disappear. These observations suggested this environment as a potential reservoir for bacteria with possible important health implications.