This work aims to put forward the role of multiwalled carbon nanotubes (MWCNTs) surface functionalization on the enhancement of thermoelectric (TE) power factor of new nanocomposite-based polypyrrole/surface modified multiwalled carbon nanotubes (PPy/MWCNTs), prepared by a facile in-situ oxidative polymerization process. In fact, MWCNTs’ content was fixed to ∼11 wt%, and their surfaces were respectively modified with different functional groups (benzoic acid (-D1), benzene tricarboxylic acid (-D3), -O, -COOH, -NH2 and -SH). After running all the required, spectral, structural, morphological, and thermoelectrical characterizations, it is revealed that the nanocomposites-based functionalized MWCNTs remarkably increase the Seebeck coefficient, and thus enhancing the material’s power factor. This improvement of TE power factor was attributed to the coating homogeneity and the good interaction between PPy and MWCNTs mainly through π–π stacking between the polymer chains and the nanotubes as well as electrostatic, hydrogen bonding, and electrons donor/acceptor groups interactions due to the functional groups grafted on the nanotube’s sidewall. The highest power factor value (0.51 μWm−1K−2) was obtained with PPy/MWCNTs-SH, which means an enhancement of 8 folds compared to pure PPy. Considering the content of MWCNTs and the ease of preparation process, these results might help to develop future TE materials and devices.