Current monitoring strategies based only on target-screening methods are not sufficient to fully address water contamination issues. High Resolution Mass Spectrometry (HRMS) based on non-target screening is therefore a promising monitoring tool. Wastewater, surface, and underground water samples were collected based on a geographical model correlating the sampling points with potential pollution sources (i.e. river infiltration, industrial site, WWTPs). After SPE pre-treatment, samples were analyzed with HPLC coupled with either Orbitrap-MS or QTOF-MS in order to obtain a comprehensive picture of the pollution state. Analyses were carried out using the SWATH DIA mode (QTOF) and full-scan followed by a top-5 ddMS2 (Orbitrap), allowing an extensive detection of every detectable compound. In addition to vendor software, data were processed using mzMine 2 and MS-DIAL, and evaluated by multivariate statistical analysis. Cluster and Principal Component Analysis were also used to understand the contamination trends among the different water bodies investigated. A total of 649 compounds have been identified and introduced in the NORMAN European Database.