Microplastics and nanoplastics are hazardous to ecosystems, wildlife, and through seafood, also for human health. Due to biological, chemical, and physical characteristics, nanoplastics can slip through cell membranes, being even more toxicologically important than microplastics. Thermal Desorption - Proton Transfer Reaction - Mass Spectrometry was used to analyze mussels from the Apulian region, Italy. All the analyzed organisms have plastics (values ranging from 10 to 187 ng of microplastics and nanoplastics per dry weight mg). The highest mass of plastics was detected in the size groups >2.2 µm (218 ng per dry weight mg) and 20–200 nm (187 ng per dry weight mg). Upscaling data we estimated that people in Europe could ingest more than 2 mg of nanoplastics per year through seafood consumption. The detected presence of nanoplastics in farmed mussels here presented contributes to establishing a baseline for monitoring these pollutants.