The recently‐increasing interest in coinage metal clusters stems from their photophysical properties, which are controlled via heterometallation. Herein, we report homometallic AgI46S13 clusters protected by octahedral fac‐[Ir(aet)3] (aet=2‐aminoethanethiolate) molecules and their conversion to heterometallic AgI43MI3S13 (M=Cu, Au) clusters. The reactions of fac‐[Ir(aet)3] with Ag+ and penicillamine produced [Ag46S13{Ir(aet)3}14]20+ ([1]20+), where a spherical AgI46S13 cluster is covered by fac‐[Ir(aet)3] octahedra through thiolato bridges. [1]20+ was converted to [Ag43M3S13{Ir(aet)3}14]20+ ([1M]20+) with an AgI43MI3S13 cluster by treatment with M+, retaining its overall structure. [1]20+ was photoluminescent and had an emission band ca. 690 nm that originated from an S‐to‐Ag charge transfer. While [1Cu]20+ showed an emission band with a slightly higher energy of ca. 650 nm and a lower quantum yield, the emission band for [1Au]20+ shifted to a much higher energy of ca. 590 nm with an enhanced quantum yield.