The aim of the present paper was to develop a multiresidue method based on GC×GC-TOF/MS in order to investigate changes induced by cooking in the composition of a complex food matrix spiked with 226 dioxin-related micropollutants. In a first step, a GC×GC-TOF/MS method was developed to achieve a satisfactory separation of the 209 PCBs and the 17 toxic PCDD/Fs in hexane. The best GC×GC-TOF/MS conditions determined according to peak shape (width and symmetry) and resolution enabled to separate 206 dioxin-related micropollutants. Starting with meat as a model matrix, the second step enabled to set up procedures for both micropollutant spiking and sample preparation. The later included accelerated solvent extraction (ASE), centrifugal evaporation and gel permeation chromatography (GPC). Recoveries in the acceptable range of 70–130% and satisfactory standard deviations (≤10%) were obtained for most of the compounds studied. Limits of detection of the GC×GC-TOF/MS method ranged between 50 and 100 pg/g of spiked fresh meat for PCBs and between 65 and 227 pg/g for PCDD/Fs. Finally, the multiresidue method was implemented to assess the modulating influence of cooking on meat content on the 206 dioxin-related micropollutants.