Isomerism of atomically precise noble metal nanoclusters provides an excellent platform to investigate the structure–property correlations of metal nanomaterials. In this study, we performed density functional theory (DFT) and time‐dependent (TD‐DFT) calculations on two Au21(SR)15 nanoclusters, one with a hexagonal closed packed core (denoted as Au21hcp), and the other one with a face‐centered cubic core (denoted as Au21fcc). The structural and electronic analysis on the typical Au–Au and Au–S bond distances, bond orders, composition of the frontier orbitals and the origin of optical absorptions shed light on the inherent correlations between these two clusters. [ABSTRACT FROM AUTHOR]