The influence of Y2O3 nanolayers on thermoelectric performance and structure of 2% Al-doped ZnO (AZO) thin films has been studied. Multilayers based on five 50 nm thick AZO layers alternated with few nanometers thick Y2O3 layers were prepared by pulsed laser deposition on Al2O3 single crystals by alternate ablation of AZO target and Y2O3 target. The number of laser shots on Y2O3 target was maintained very low (5, 10 and 15 pulses in three separate experiments. The main phase (AZO) presents polycrystalline orientation and typical columnar growth not affected by the presence of Y2O3 nanolayers. The multilayer with 15 laser shots of Y2O3 showed best thermoelectric performance with electrical conductivity σ = 48 S/cm and Seebeck coefficient S = -82 μV/K, which estimate power factor (S2·σ) about 0.03 × 10-3 W m-1 K-2 at 600 K. The value of thermal conductivity (κ) was found 10.03 W m-1 K-1 at 300 K, which is one third of typical value previously reported for bulk AZO. The figure of merit, ZT = S2·σ·T/κ, is calculated 9.6 × 10-4 at 600 K. These results demonstrated the feasibility of nanoengineered defects insertion for the depression of thermal conductivity.