Anthropogenic pressures can adversely affect the quality of coastal sediment posing at risk human health and the ecosystem. The Southeastern Tyrrhenian Sea (STS) coast (Italy) is still largely unexplored under this point of view. This study investigated for the first time in the area the seasonal variation and potential impact of selected metals (Cd, Cr, Cu, Ni, and Pb) and tributyltin (TBT) from sediment samples collected along the STS coast (Casalvelino Marina, Casalvelino Bay, Acciaroli Marina and Acciaroli Bay) in the perspective of Water Framework Directive and Marine Strategy Framework Directive. Data were compared to the contamination background levels of Punta Licosa reference site considering elemental enrichment factors (EFs) and single substance- and mixture-based risk characterisation ratios. Further, data were discussed considering the review of Southern Tyrrhenian Sea sediment quality. Results evidenced an increase of contamination levels from March to October showing that marinas are more impacted than bays. Sediment EFs highlighted that contamination levels were always greater than the reference site like risk characterisation ratios, suggesting the presence of potential threats. The sediment quality database generated after literature review revealed a similar situation for the whole Southern Tyrrhenian Sea.