Yuan Li's team discovered that heteroatom engineering, by substituting terminal iodine and backbone oxygen atoms in molecular junctions, dramatically enhances the thermoelectric power factor (PF) through resonant states near the Fermi level, achieving a PF improvement exceeding five orders of magnitude in HS-(C?O)?-C?-I compared to conventional alkanethiolates. This breakthrough highlights the critical role of chemical structure modulation in advancing nanoscale thermoelectric devices for efficient energy conversion. The work demonstrates unprecedented simultaneous enhancement of electrical conductivity and Seebeck coefficient via tailored molecular design.