The high‐temperature limitations of single‐atom catalyst (SAC) synthesis, primarily thermal aggregation and low metal loadings, are overcome by a novel room‐temperature metal‐exchange strategy. We leverage the weak Zn–N coordination in high‐loading Zn SACs (12.1 wt%, synthesized via controlled ZIF‐8 pyrolysis) as a platform for the facile exchange with a broad range of metals (Mn, Fe, Co, Ni, Cu, Ru, Pt, up to 12.67 wt%) and the creation of multi‐metallic species. This ambient‐temperature approach significantly reduces aggregation, enhancing the exposure of catalytic active sites and delivering superior multi‐enzyme‐like activities (catalase, peroxidase, oxidase). Our work not only provides a scalable, low‐temperature route to high‐performance SACs but also reveals crucial insights into the stability of SACs under metal‐ion conditions.