Organometallic nanozymes, organometallics of which mimic the cofactor of natural enzymes, have the advantages of tunable catalytic activity, high stability, and material variety. By assembling organometallics (catalytic site) on inorganic nanoparticles (support), organometallic nanozymes have been rationally designed, but modulating their assembly and activity remains a tough challenge. Here, we construct a photo-modulated organometallic nanozyme by anchoring azobenzene-modified triethylenetetramine (Azo-N4) to the surface of β-cyclodextrin-capped gold nanoparticles (AuNP@CDs) through host–guest interaction, followed by Zn(II) coordination to form organometallics. The catalytic site derives from the outer organometallic layer. The nanozyme catalyzes the hydrolysis of 4-nitrophenyl acetate to 4-nitrophenol and the catalytic signal is used to detect Zn(II). Due to the photoisomerization of azobenzene, the supramolecular assembly of host–guest interaction is modulated by light. The disassembly leads to cascade catalysis of AuNP@CDs-Azo-N4-Zn and the recovery of AuNP@CDs. Our study provides a new idea and reference for the rational design and activity modulation of organometallic nanozymes.