We report a remarkable sensitivity of self-assembled structures of giant surfactants on their chemical compositions and molecular topology, which facilitate the engineering of various nanophase-separated structures with sub-10 nm feature sizes. Two classes of giant surfactants composed of various functionalized polyhedral oligomeric silsesquioxane (POSS) heads tethered with one or two polystyrene (PS) tails were efficiently prepared from common precursors of vinyl-substituted POSS PS conjugates via one-step "thiol-ene" postpolymerization functionalization. With identical molecular weights of the PS tails, the resulting giant surfactants exhibited distinct highly ordered phases, as evidenced by small-angle X-ray scattering and transmission electron microscopy observations. Moreover, comparison between the topological isomers revealed that the self-assembled structures are also highly sensitive to molecular topology. Introduction of two PS tails with half-length not only shifted the boundaries between different ordered phases but also altered the packing configurations of the functional POSS cages, leading to further reduced feature sizes of the self-assembled nanodomains. Interestingly, a lower order disorder transition temperature was also observed in the fluorinated F13POSS tethered with two PS17 tails, compared to its topological isomer composed of F13POSS tethered with one PS35 tail, indicating that the topological effect also existed in phase transition behaviors. These results provide insights to rationally design and precisely tailor self-assembled structures by controlling both primary chemical compositions and molecular topology in POSS-based giant surfactants.