Polyhedral oligomeric silsesquioxane (POSS) is an organic‐inorganic hybrid molecule with two structural variations, closed‐ and open‐cage configurations, referred to as completely condensed POSS (CC‐POSS) and corner‐opened POSS (CO‐POSS), respectively. In this study, we synthesized 12 dimers by combining CC‐ and CO‐POSS variants decorated with isobutyl or phenyl substituents to explore their structure‐property relationships. The choice of substituents, both at the cage vertices and open sites, significantly affected the thermal and optical properties of the materials. Modifying the substituents on CO‐ and CC‐POSS, which are isomers, led to significant alterations in the material properties. Notably, isomer‐bearing carbazole substituents exhibited a substantially higher quantum yield (0.32) than its counterpart isomer (0.13), underscoring the crucial role of structural nuances in determining material performance. These results offer valuable insights for the design of novel silsesquioxane‐based materials.