This paper reports the results of an investigation of vapor molecule sorption at different types of nanostructured nanoparticle films. Core-shell nanoparticles of two different core sizes, AU2-nm and Au5-nm, and molecular linkers of two different binding properties, 1,9-nonanedithiol and 11-mercaptoundecanoic acid, are utilized as building blocks for constructing chemically sensitive interfaces. The work couples measurements of two different transducers, interdigitated microelectrodes and quartz crystal microbalance, to determine the correlation of the electronic resistance change and the mass loading with vapor sorption. The responses to vapor sorption at these nanostructured interfaces are demonstrated to be dependent on the core size of nanoparticles and the chemical nature of linking molecules. The difference of molecular interactions of vapor molecules at the nanostructured interface is shown to have a significant impact on the response profile and sensitivity. For the tested vapor molecules, while there are small differences for the sorption of nonpolar and hydrophobic vapor molecules, there are striking differences for the sorption of polar and hydrophilic vapor molecules at these nanostructured interfacial materials. The implication of the findings to the delineation of design parameters for constructing core-shell nanoparticle assemblies as chemically sensitive interfacial materials is also discussed.