A reliable identification of suspected organic micropollutants at trace levels in environmental samples requires integrated analytical workflows based on liquid chromatography coupled to high resolution mass spectrometry. Then the challenge for suspected screening strategy is to develop a systematic and generalizable workflow including i) the acquisition of general information on suspected compounds, with spectral and data chromatographic data, and ii) the confrontation of the acquired data to those in available libraries and software tools. A combined targeted and suspected screening strategy has been developed in our laboratory and applied to waters from different aquatic environment (waters collected in waste water treatment plants or in agricultural watersheds, both contaminated with organic micropollutants and metabolites). Analysis of parent and degradation products were performed on a Waters ACQUITY H-Class UPLC system coupled to a Xevo G2 S high resolution mass spectrometer using a QTOF technology. The separation was performed on a C18 HSS-T3 column after direct injection of the waters in order to avoid losses due to pre-treatments. Acquired raw data were processed quantitatively for parent compounds using TargetLynx and qualitatively for suspect compound identification using ChromaLynx applications manager for MassLynx 4.1 software. Such strategy allowed combining a classical targeted analysis with a quantitative approach and a retrospective database comparison for suspected screening of a wide range of compounds. The application of such a workflow needs the preselection of relevant compounds, i.e. suspected to be present in the studied aquatic environments and that are supposed to have an impact on the water quality. We present some examples of application to real samples, and also identify the current scientific gaps and research needs to progress in such suspected screening strategies.