To effectively treat gastric cancer, we innovatively attempted to develop a metal agent to integrate immunotherapy and chemotherapy by dual targeting the cellular components in the tumor microenvironment (TME) based on the specific residue of human serum albumin (HSA) nanoparticles (NPs). We synthesized a series of Au(III) α-N-heterocyclic thiosemicarbazone compounds and obtained a Au agent (5b) with remarkable cytotoxicity to gastric cancer cells; moreover, we successfully constructed a novel HSA-5b complex NP delivery system. Importantly, the in vivo results showed that 5b/HSA-5b NPs effectively inhibited gastric tumor growth and HSA-5b NPs enhanced the therapeutic efficiency, bioavailability, and targeting ability compared with those of 5b alone. Furthermore, the in vitro/in vivo results revealed that 5b/HSA-5b NPs could integrate chemotherapy and immunotherapy by synergistically attacking two different cellular components in TME at the same time, namely, polarizing the tumor-associated macrophages and inducing apoptosis of gastric cancer cells.