SWATH-MS offers a robust data-independent acquisition method for complex proteomics and metabolomics. This study presents a detailed non-target screening workflow utilizing SWATH-MS to detect and analyze emerging contaminants (ECs) in aquatic environments. Our workflow, covering peak picking, alignment, prioritization, structure identification, and quantification, effectively identified all qualifying peaks from 298 standard compounds with different concentrations, discarding any that did not meet the criteria. In extracts of real water samples spiked at 100 and 10 ng/mL, our workflow prioritized 2083 and 1328 features, respectively. Following structure identification, these features were assigned confidence levels ranging from 1 to 5. Of these, 215 and 92 spiked standards achieved level 1. The remaining standards were not recognized as level 1 due to low intensities or poor peak shapes that failed to meet certain criteria. Additionally, using fragment ion peak areas for quantification significantly improved the linearity of standard curves, enhancing R