The Mediterranean Sea water bodies are ones of the most polluted, especially with microplastics. As the seafloor is the ultimate sink for litter, it is considered a hotspot for microplastic pollution. We provide an original analytical development based on the coupling of tandem mass spectrometry to pyrolysis-gas chromatography to improve the detection of plastic contamination in marine organisms. Due to the high selectivity of the mass spectrometer, a straightforward sample preparation consists uniquely of potassium hydroxide digestion. The quantification of six common polymers is possible in one run. The method was applied to analyze the plastic content from 500 μm down to 0.7 μm in the whole body of seven benthic species with variable feeding modes. Plastic was detected in all samples, with an almost systematic detection of polypropylene and polyethylene. Our method presents a major development in determining the levels of plastic contaminations in samples with rich organic matter content.