Abstract Integrating multiple mechanisms to maximize photothermal conversion efficiency is a significant strategy but remains challenging to construct therapeutic agents toward photothermal tumor treatment. Here, an approach to synthesize asymmetric Bi 2 Se 3 /CdSe‐Au hierarchical nanorods with excellent photothermal conversion is reported. Ag wetting‐layer is firstly grown to help overcome the interfacial lattice mismatch and promote the site‐selective growth of AgCdSe onto one end or side surface of Au nanorods. Subsequently, extraction of Ag + ions out of lattice is observed during cation exchange reaction and epitaxial growth of Bi 2 Se 3 shell. Bi 2 Se 3 /CdSe heterojunction with type‐II band alignment is formed and located at the plasmonic hotspots of Au nanorods, which experiences enhanced light absorption and accelerates the charge separation of photo‐excited carriers. Under excitation of near‐infrared 808 nm laser, the matchstick‐like Bi 2 Se 3 /CdSe‐Au nanorods show an excellent photothermal conversion, with 4.3 times temperature increment ( Δ T ) than that of bare Au nanorods. Moreover, in vitro and in vivo experiments verify them as excellent photothermal therapeutic agents.