Abstract: Identifying characteristic pollutants at pesticide-contaminated sites is challenging due to the complex composition and diversity of pesticide residues and their transformation products. To address this issue, this study proposes a novel screening framework that integrates targeted and non-targeted analytical approaches using ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) and ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS). A comprehensive scoring system based on 12 evaluation indicators-including structural identification confidence, relative peak area, overall detection frequency, and metabolite identification etc., was established to improve the accuracy and efficiency of characteristic pollutant identification. A pesticide-contaminated site in Jiangsu Province was selected as a case study. Targeted analysis detected nine pesticides, while non-targeted analysis identified eleven pesticides and related metabolites. These include six fungicides (carbendazim, azoxystrobin, pyraclostrobin, thiophanate-methyl, tebuconazole, and difenoconazole), one metabolite (benzimidazole), three herbicides (atrazine, pretilachlor, and flumioxazin), and one insecticide (paclobutrazol). Based on the proposed framework, carbendazim, atrazine, and tebuconazole were identified as the characteristic pollutants at the study site. This approach provides a practical strategy for the systematic identification of characteristic pollutants at pesticide-contaminated sites.