Coupling between iso(thio) cyanates and amines, alcohols, and thiols to yield (thio) urea/urethane in the gas phase is important for the vacuum deposition processes of functional organic thin films such as molecular layer deposition or chemical vapor deposition. In this study, the kinetics and thermodynamics of 12 reactions between bifunctional reactants containing -NCO/-NCS and -NH2/-OH/-SH moieties were calculated using double-hybrid density functional theory to find systematic structure-reactivity relationships. The activation energy for the proton-transfer step was correlated with the basicity of the nucleophile/Bronsted acid reactants, while the exothermicity of the coupling reaction depends on whether the other functionality is -NCO or -NCS. Analysis of the transition states revealed that the location of the transition state is affected by the basicity of the reactants. Vibrational and electronic spectra of the product were obtained to help future experimental investigations.