As the aquaculture sector significantly expanded worldwide in the past decades, the concept of sustainable aquaculture has developed with the challenge of not only maximizing benefits but also minimizing the negative impacts on the environment assuring, at the same time, food security. In this framework, monitoring and improving the microbiological water quality and animal health are a central topic. In the present study, we evaluated the seawater microbiological quality in a mariculture system located in a Mediterranean coastal area (Northern Ionian Sea, Italy). We furnished, for the first time, a microbial inventory based on conventional culture-based methods, integrated with the 16S rRNA gene metabarcoding approach for vibrios identification and diversity analyses, and further implemented with microbial metabolic profiling data obtained from the Biolog EcoPlate system. Microbiological pollution indicators, vibrios diversity, and microbial metabolism were determined in two different times of the year (July and December). All microbial parameters measured in July were markedly increased compared to those measured in December. The presence of potentially pathogenic vibrios is discussed concerning the risk of fish disease and human infections. Thus, the microbial inventory here proposed might represent a new multiparametric approach for the suitable surveillance of the microbial quality in a mariculture system. Consequently, it could be useful for ensuring the safety of both the reared species and the consumers in the light of sustainable, eco-friendly aquaculture management.