Transition metal dichalcogenides (TMDs) have received considerable attention due to their strong absorption in the near-infrared (NIR) region, strong spin-orbit coupling, and excellent photothermal conversion efficiency (PCE). Herein, CoFeMn dichalcogenide nanosheets (CFMS NSs) are prepared via facile vulcanization of a lamellar CoFeMn-layered double hydroxide (LDH) precursor followed by polyvinyl pyrrolidone modification (to give CFMS-PVP NSs), and found to show excellent photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) performance. The as-prepared CFMS-PVP NSs inherit the ultrathin morphology of the CoFeMn-LDH precursor and exhibit an outstanding photothermal performance with a η of 89.0%, the highest PCE reported to date for 2D TMD materials. Moreover, 50% of maximum catalytic activity (Michaelis-Menten constant, K m) is attained by CFMS-PVP NSs with 0.26 × 10-3 m H2O2 at 318 K, markedly lower than the endogenous concentration of H2O2 inside tumor cells. In addition, complete apoptosis of HepG2 cancer cells and complete tumor elimination in vivo are observed after treatment with CFMS-PVP NSs at a low dose, substantiating the NSs’ remarkable PTT/CDT efficacy. This work provides a new and facile approach for the synthesis of high-quality multicomponent TMD nanosheets with precise process control, the potential for mass production, and outstanding performance, providing great promise in cancer theranostics.