Stir bar sorptive extraction (SBSE) and thermal desorption followed by capillary gas chromatography coupled to mass spectrometry (SBSE–TD–GC–MS) was applied to the simultaneous determination of ultra-traces of 16 polycyclic aromatic hydrocarbons (PAHs), 12 polychlorinated biphenyls (PCBs), 6 phthalate esters (PEs) and 3 nonylphenols (NPs) in water samples. The parameters that could affect the sorption–desorption efficiency were studied. A Plackett–Burman design was used for the screening of the main effects of the experimental parameters related to the desorption step (desorption time, desorption temperature, desorption flow, cryo-focusing temperature and vent pressure). Afterwards, two central composite designs were used to find the optimal process settings for the extraction and desorption steps. The best analytical compromise conditions for the simultaneous determination of analytes from spiked water samples were found to be: sample volume (20 mL), sodium chloride addition (30%), methanol addition (20%), desorption time (10 min), desorption temperature (300 °C), desorption flow (23 mL min −1), cryo-focusing temperature (−50 °C) and vent pressure (7 psi). Remarkable recovery, repeatability and reproducibility were attained. Furthermore, excellent linearities ( r 2 = 0.959–0.999) and low detection limits (0.1–10 ng L −1) were also achieved for the congeners studied. The proposed methodology was applied for the simultaneous determination of PAHs, PCBs, PEs and NPs in sea and estuarine waters. The influence of humic acids on the recovery was also studied.