Albeit considerable attention to the fast‐developing organic thermoelectric (OTE) materials due to their flexibility and non‐toxic features, it is still challenging to design an OTE polymer with superior thermoelectric properties. In this work, two “isomorphic” donor–acceptor (D–A) conjugated polymers are studied as the semiconductor in OTE devices, revealing for the first time the internal mechanism of regioregularity on thermoelectric performances in D–A type polymers. A higher molecular structure regularity can lead to higher crystalline order and mobility, higher doping efficiency, order of energy state, and thermoelectric (TE) performance. As a result, the regioregular P2F exhibits a maximum power factor (PF) of up to 113.27 µW m−1 K−2, more than three times that of the regiorandom PRF (35.35 µW m−1 K−2). However, the regular backbone also implies lower miscibility with a dopant, negatively affecting TE performance. Therefore, the trade‐off between doping efficiency and miscibility plays a vital role in OTE materials, and this work sheds light on the molecular design strategy of OTE polymers with state‐of‐the‐art performances.