Although a homometallic (isotopic metal) exchange reaction has been reported, the in-depth understanding of the interaction between a metalloid cluster and the homometal (representing the same metal element as the metalloid cluster) thiolate is quite limited, especially at the atomic level. Herein, based on Ag-44(SR)(30) (where SR represents 4-mercaptobenzoic acid), we report a facile approach for investigating the metalloid cluster-homometal thiolate interaction at the atomic level, i.e., isotopic exchange in the Ag metalloid cluster. Since such a reaction takes no account of the enthalpy change-related heterometal (representing a different metal element) exchange, the intrinsic metalloid cluster-homometal thiolate interaction can be thoroughly investigated. Through analyzing the ESI-MS (electrospray ionization mass spectrometry) and MS/MS (mass/mass spectrometry) results of the reversible conversion between Ag-107(44) (SR)(30) and Ag-109(44) (SR)(30), we observed that all Ag atoms are exchangeable in the Ag-44 (SR)(30) template. In addition, through analyzing the ESI-MS results of the interconversion between Ag-107(29) (BDT)(12) (TPP)(4) and Ag-109(29) (BDT)(12) (TPP)(4), we demonstrated that the metal exchange in the Ag-29(BDT)(12) (TPP)(4) metalloid cluster should be a shell -> kernel metal transfer process. Our results provide new insights into the metalloid cluster reactivity in the homometal thiolate environment, which will guide the future preparation of metalloid clusters with customized structures and properties.