Abstract: To address the growing need for multi-class, high-throughput monitoring of veterinary drug residues in poultry egg products and the deficiencies of existing methods in detection scope, sensitivity and matrix applicability, a comprehensive method for the simultaneous determination of 53 banned and restricted veterinary drugs from 9 classes in chicken, duck, goose, and pigeon eggs was developed. The sample preparation procedure was systematically optimized, including the extraction solvent and QuEChERS purification sorbents. The optimized method involved extraction with 0.2 mol/L Na₂EDTA-Mcllvaine buffer solution and acetonitrile, followed by cleanup using a composite of C₁₈, NH₂, and PSA sorbents. The target analytes were then determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that all 53 veterinary drugs exhibited good linearity (R²≥0.9903). The limits of detection (LOD) and the limits of quantification (LOQ) ranged from 1 μg/kg to 4 μg/kg and 2 μg/kg to 10 μg/kg, respectively, which all met or exceeded the maximum residue limits specified in the GB 31650.1-2022 “National food safety standard- Maximum residue limits for 41 veterinary drugs in foods”. Average recoveries at three spiked levels ranged from 61.2% to 113.6%, with relative standard deviations (RSDs) between 0.1% and 18.9%. The developed method was successfully applied to screen 53 batches of actual poultry egg samples, and eight batches were found to contain target compounds, and the results were consistent with those obtained by the national standard methods. The proposed method successfully solves the problem of simultaneous detection caused by large differences in the physical and chemical properties of drugs and complex poultry egg matrices, and has the advantages of simple sample pretreatment, fast analysis speed (10 min), high sensitivity, accuracy and reliability. It is suitable for high-throughput screening and precise supervision of multi-class veterinary drug residues in various poultry egg matrices.