Per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants in many industrial and consumer products, such as pesticides, textiles, and food packaging. Although PFAS are widely used, knowledge about their occurrence in ambient particulate matter and the associated health risks remains limited. The objective of this study was to develop a sensitive, accurate, and simple method for analysing 24 PFAS compounds in total suspended particulate matter (TSP) by HPLC-MS/MS. The target compounds included 7 perfluoroalkane sulfonic acids, 11 perfluoroalkyl carboxylic acids, and 6 perfluoroalkyl acid precursors. Various instrumental parameters were optimized, including declustering potential (DP) and collision energy (CE). The ultrasound-assisted extraction conditions for dust-bound PFAS were optimized by varying the volume of methanol (MeOH), extraction time, and temperature. The optimal condition was determined to be extraction with 4 mL of MeOH at 40 °C for 10 minutes, repeated three times. Method validation results demonstrated sub-ng/L limits of quantification (LOQs) ranging from 0.01-0.14 ng/mL, with high recoveries near the LOQs (95.5% to 114.40%) and high repeatability with %RSD values ranging from 0.1% to 12.6%. The analytical procedure was subsequently applied to assess the level of PFAS contamination in TSP samples in Ho Chi Minh City. The results showed that 22 of the 24 targeted PFAS compounds were detected in the TSP samples, highlighting the significant presence of these pollutants in the megacity.