In this work the development and validation of a new procedure for the simultaneous determination of 9 nitro and polycyclic musk compounds: musk ambrette (MA), musk ketone (MK), musk mosken (MM), celestolide (ADBI), phantolide (AHMI), tonalide (AHTN), traseolide (ATII), cashmeran (DPMI) and galaxolide (HHCB) in environmental water samples (estuarine and wastewater) using microextraction by packed sorbent (MEPS) followed by large volume injection-gas chromatography–mass spectrometry (LVI-GC–MS) was carried out. Apart from the optimization of the different variables affecting MEPS (i.e., nature of the sorbent, nature of the solvent elution, sample load, and elution/injection volume) extraction recovery was also evaluated, not only for water samples but also for environmental water matrices such as estuarine and waste water. The use of two deuterated analogs ([²H₃]-AHTN and [²H₁₅]-MX) was successfully evaluated in order to correct matrix effect in complex environmental matrices such as influent samples from wastewater treatment plants. Method detection limits (MDLs) ranged from 5 to 25 ng L⁻¹, 7 to 39 ng L⁻¹ and 8 to 84 ng L⁻¹ for influent, effluent and estuarine samples, respectively. Apparent recoveries were higher than 75% for all target compounds in all the matrices studied (estuarine water and wastewater) and the precision of the method, calculated as relative standard deviation (RSD), was below 13.2% at 200 ng L⁻¹ concentration level and below 14.9% at low level (20 ng L⁻¹ for all the target analytes, except for AHTN which was set at 40 ng L⁻¹ and HHCB at 90 ng L⁻¹, due to the higher MDL values presented by those target compounds). Finally, this MEPS procedure was applied to the determination of the target analytes in water samples, including estuarine and wastewater, from two estuaries, Urdaibai (Spain) and Adour (France) and an established stir-bar sorptive extraction-liquid desorption/large volume injection-gas chromatography–mass spectrometry (SBSE-LD/LVI-GC–MS) method was performed in parallel for comparison. Results were in good agreement for all the analytes determined, except for DPMI.