The interfacial carrier scattering was thought to be ineffective in enhancing thermoelectric (TE) properties of polymer hybrids and there was also a lack of fundamental understanding of carrier scattering at polymer/polymer interfaces. Here we unravel the mechanism behind the role of polymer/polymer interfacial scattering on the TE properties through integration of computation and experiments. We discover that the effect of interfacial scattering at polymer/polymer interfaces on TE properties of polymer hybrids is strongly dependent on the carrier mobility of host polymers besides interfacial barriers. Only when the host carrier mobility is above a threshold, the effect of interfacial scattering on TE enhancement can be significant. Simulation suggests that the host mobility threshold is ~1cm2 V−1 s−1 for PEDOT-based polymers. The polymer hybrid system of poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires/PEDOT was successfully employed to verify the theoretical results. These findings offer groundbreaking knowledge on polymer/polymer interfacial carrier-transport and will advance the design and fabrication of high-efficiency organic thermoelectric materials.