Precise synthesis of nanobuilding blocks with accurately positioned functional groups presents a daunting challenge. Herein, a practical synthesis and thorough characterization of a series of T8-polyhedral oligomeric silsesquioxane (POSS) di- and triadducts is reported. Upon addition of triflic acid across the double bonds in octavinylPOSS (V8T8) followed by hydrolysis, the cubic symmetry of the T8-POSS cage (Oh) is broken into C2v (ortho-), C2v (meta-), and D3d (para-) for diadducts and further to Cs (oom-), Cs (omp-), and C3v (mmm-) for triadducts in a stochastic fashion. Their structures and regioconfigurations have been unambiguously demonstrated by 1H, 13C, and 29Si NMR spectroscopy, as well as MALDI-TOF mass spectrometry. The assignment of the diadducts was further corroborated by converting each individual diadduct into triadduct(s), the structure of which is controlled by the symmetry of the precursor. Except for the C3v triadduct, they can all be prepared in synthetically useful quantities. The presence of two types of highly reactive and mutually orthogonal functional groups facilitates further modification into complex nanostructures and composite materials. These unique regioisomers provide a versatile platform for constructing giant molecules and Janus silsesquioxanes.