Theoretical and experimental methods were integrated to investigate the structures of H-(CH3OH)m(H2O) n clusters for m + n = 5 and 6. An effective theoretical approach is presented to search for extensive sets of structural isomers using an empirical model and substitution schemes. Stable isomers were then reoptimized by the B3LYP level of computations with the 6-31+G* basis set. Canonical averages of these structural isomers were analyzed by harmonic superposition approximation (HSA) to study their finite temperature behavior and enable quantitative comparisons with experimental results. Thermal energy is found to have a significant effect on the structure of these clusters. Our calculations show that cyclic isomers are preferred at low temperature, while linear and tree forms become more favorable at high temperature (>200 K). Furthermore, we found that proton can reside on both water and methanol ion cores and the proton switch is associated with morphology change. Experimental IR spectra in the free OH stretching region were also obtained and compared with calculated spectra.