This paper reports a facile, modular, and efficient approach to the synthesis of shape amphiphiles with a hydrophobic polymer chain as the tail and a polar, compact, functional polyhedral oligomeric silsequioxane (POSS) nanoparticle as the headgroup. A poly(l-lactide) (PLLA) chain was grown from monohydroxyl-functionalized heptavinyl POSS (VPOSS-OH) with controlled molecular weight and narrow polydispersity by stannous octoate-mediated ring-opening polymerization of l-lactide. To impart tunable polarity and functionality to the headgroup, various functional groups, such as carboxylic acids, hydroxyl groups, and sugars, were attached to the POSS cage in high efficiency by thiol-ene "click" chemistry, which provides a straightforward and effective approach to synthesize shape amphiphiles with diverse head surface chemistry. The polymers have been fully characterized by 1H NMR, 13C NMR, FT-IR spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography. These functional POSS can serve as versatile nanobuilding blocks in the "bottom-up" construction of nanoscale structures and assemblies that may exhibit rich self-assembling behavior and potentially useful physical properties.