Potential biomedical applications of gold nanoparticles have increasingly been reported with great promise for diagnosis and therapy of several diseases. However, for such a versatile nanomaterial, the advantages and potential health risks need to be addressed carefully, as the available information about their toxicity is limited and inconsistent. Atomically precise gold nanoclusters (AuNCs) have emerged to overcome this challenge due to their unique features, such as superior stability, excellent biocompatibility, and efficient renal clearance. Remarkably, the elucidation of their structural and physicochemical properties provided by theory–experiment investigations offers exciting opportunities for site‐specific biofunctionalization of the nanoparticle surface, which remains a significant concern for most of the materials in the biomedical field. This concept highlights the advantages conferred by atomically precise AuNCs for biomedical applications and the powerful strategy combining computational and experimental studies towards finding an optimal biocompatible AuNCs‐based nanosystem.