In this research paper, we report a hyphenated technique based on ultra-high performance liquid chromatography–tandem mass spectrometry for the determination of twelve Perfluorinated Alkylated Substances in surface and groundwater samples from Lombardia Region during the monitoring activities in 2018 as new emerging and toxic pollutants. A green analytic method, developed by using an online Solid Phase Extraction coupled with UHPLC-MS/MS and previously validated, was applied for 4992 determinations conducted on 416 samples from 109 different sampling stations. Among the results, PFOS, PFOA, PFBA, PFBS, PFPeA and PFHxA were identified as the most abundant analytes detected. PFASs concentrations, in most cases, were below the limits of quantification and, in the cases where the limits of quantification have been exceeded, the values found were lower than Italy directive. PFOS is an exception and in fact this compound was detected in 76% of analyzed samples (surface and ground waters). Solid phase extraction with high performance liquid chromatography–tandem Mass Spectrometry has proved to be a very good Hyphenated techniques able to detect low concentrations of pollutants in surface and groundwater samples.