Efficient engineering of solid dispersions stagnates by the current inability to establish the mode of drug distribution on a molecular level at a low drug load. This study describes the application of fluorescence resonance energy transfer (FRET) to characterize the mode of incorporation of dispersed lipophilic molecules in a solid matrix. Two different lipophilic fluorophores (donor and acceptor) were used as model substances and were incorporated in polyvinylpyrrolidone to form solid dispersions using two different production processes: lyophilization and fusion. The efficiency of the resonance energy transfer from donor to acceptor was measured by confocal microscopy. We show that the method can be used to compare the modes of drug incorporation of solid dispersions at the nanoscale.