We have implemented high-throughput spectroscopic screening tools for the investigation of vapor-selectivity of CdSe semiconductor nanocrystals of different size (2.8- and 5.6-nm diameter) upon their incorporation in a library of rationally selected polymeric matrices. This library of resulting sensing materials was exposed to polar and nonpolar vapors in air. Each of the sensing materials demonstrated its own photoluminescence vapor-response patterns. Two criteria for the evaluation of vapor responses of the library of sensing materials included the diversity and the magnitude of sensing responses. We have found several polymer matrices that simultaneously meet these criteria. Our new sensing materials based on polymer-embedded semiconductor nanocrystal reagents of different size promise to overcome photobleaching and short shelf life limitations of traditional fluorescent organic reagent-based sensing materials.