A series of copper phthalocyanine (CuPc)-based organic small molecules were prepared through vapor-phase reaction. Nanoscale phase separation was observed with tunable CuPc and copper phthalocyaninato iodide (CuPcI) phase content by changing the iodine ratio. The Seebeck coefficient of the samples was significantly enhanced, which is considered to be attributed to the enhanced surface polarization effect due to the formation of a great number of nanoscale interfaces between the CuPc phase and the CuPcI phase. In addition, these nanointerfaces also gave rise to increased phonon scattering and therefore significantly reduced the lattice thermal conductivity of the small-molecule samples. As a result of the combination of the synergistically optimized electrical and thermal transport properties, the maximum ZT value reaches 3.0 × 10-2 at room temperature, which is among the highest values for small-molecule charge-transfer complex reported so far. Our results shed light on optimizing the thermoelectric performance of organic small molecules by introducing nanoscale phase separations and tailoring the nanoscale interfaces.