In food safety testing, simultaneous detection of multiple harmful residues is crucial because pesticide and veterinary drug residues often occur together.A method was developed for the simultaneous determination of residues of 20 pesticide and veterinary drug compounds in both buffalo and cow milk, utilizing a modified QuEChERS method combined with ultra-performance liquid chromatog.-tandem mass spectrometry (UPLC-MS/MS).The targeted analytes were efficiently extracted from milk matrixes using a 10 % formic acid solution in acetonitrile.Optimization of both pre-treatment and anal. parameters significantly enhanced the method′s sensitivity.Quantification was performed using matrix-matched calibration curves, which demonstrated exceptional linearity (R2 > 0.9990) across all analytes.Method validation, conducted with fortified blank milk samples at concentrations of 5, 10, and 50 μg/L, yielded recoveries ranging from 73.1 % to 111.6 %.The relative standard deviations for all analytes were consistently below 15 %, confirming the method′s precision.The limits of detection (LOD) and quantification (LOQ) were determined to be between 0.7 and 1.7 μg/L and 2.0 and 5.0 μg/L, resp.This method is straightforward, sensitive, accurate, and environmentally friendly, making it well-suited for the detection of multiple pesticides and antibiotics in milk.