The striped venus (Chamelea gallina) is an important economic resource in the Mediterranean Basin; this species has exhibited a strong quantitative decline in the Adriatic Sea. The aim of this work was to provide a comprehensive view of the biological status of C. gallina to elucidate the bioecological characteristics and genetic diversity of wild populations. To the best of our knowledge, this investigation is the first to perform a multidisciplinary study on C. gallina based on two omics approaches integrated with histological, ecotoxicological, and chemical analyses and with the assessment of environmental parameters. The results obtained through RNA sequencing indicated that the striped venus has a notable ability to adapt to different environmental conditions. Moreover, the stock reduction exhibited by this species in the last 2 decades seems not to have negatively affected its genetic diversity. Indeed, the high level of genetic diversity that emerged from our ddRAD dataset analyses is ascribable to the high larval dispersal rate, which might have played a "compensatory role" on local fluctuations, conferring to this species a good adaptive potential to face the environmental perturbations. These findings may facilitate the efforts of conservation biologists to adopt ad hoc management plans for this fishery resource.