A new class of luminescent molecular hybrids in which eight cyclometalated iridium(III) polypyridine complexes are grafted onto a polyhedral oligomeric silsesquioxane (POSS) unit [POSS‐{Ir(N^C)2(py‐im)}8](PF6)8 [py‐im=pyridine imine; HN^C=N‐phenylpyrazole (Hppz) (1 a), 2‐phenylpyridine (Hppy) (2 a), 2‐phenylquinoline (Hpq) (3 a)] were synthesized and characterized. On photoexcitation, the complexes showed intense and long‐lived orange‐red to red emission in fluid solutions at room temperature and in low‐temperature glasses. The photophysical properties including aggregation‐induced emission and biological properties of these complexes were studied and compared with those of their POSS‐free counterparts [Ir(N^C)2(py‐im)](PF6) [HN^C=Hppz (1 b), Hppy (2 b), Hpq (3 b)]. The (photo)cytotoxicity of the complexes was examined by the MTT assay, and their cellular uptake and intracellular localization were investigated by inductively coupled plasma‐mass spectrometry and laser‐scanning confocal microscopy.