Polyhedral oligomeric silsesquioxanes (PUSS) have been incorporated into a wide range of polymers over the past two decades in an attempt to enhance their thermal and mechanical properties. Properties of POSS/polymer blends/composites are highly dependent on the uniformity of POSS dispersion and thus are particularly sensitive to the magnitude of interaction between POSS and added fillers/polymers. Methods to characterize these interactions in terms of solubility parameters have been recently examined in the literature using group contribution calculations. The present work presents a method for measuring three-dimensional Hansen solubility parameters for polymers and POSS which allows for the direct calculation of interaction potentials. These measured solubility parameters predict POSS/polymer interactions more accurately than group contribution calculations and accurately predict the uniformity of PUSS dispersion and the resultant property enhancements.