This article reports the fabrication of a smart biomimetic enzyme system, which incorporates a pH-responsive chemodynamic therapy (CDT) combined with a photothermal (PTT) therapy approach in resolving the high recurrence rate of deadly cancers. The resulting enzyme system comprises copper sulfide (CuS) nanoparticle (NP) cores as Fenton-like catalysts, and a photothermal-active generation 5 poly(amidoamine) (G5) dendrimer as a template for the entrapment of Cu NPs and the compression of glucose oxidase (GOD). GOD is introduced to produce H O necessary in the sequential Fenton-like reaction, and this generates hydroxyl radicals that kill the cancerous cells. Polyethylene glycol is added to the system to improve biocompatibility. Mechanism study suggests that the constructed CuS/G5-GOD-based system has a better Fenton-like catalytic activity than a Fe O -GOD-based system. This allows the further inhibition on the residual tumors from recurrence and metastasis through CDT after being treated by PTT. The developed smart nanoscale biomimetic system shows high efficiency for breast cancer suppression from recurrence and metastasis by combining PTT with a pH-responsive CDT. It has the potential to resolve the essential issue of cancer recurrence after its initial clinic treatment.