Steady-state and time-resolved infrared (IR) studies of cyclotetramethylene tetranitramine (HMX) were carried out, using the asymmetric nitro-stretch as probe, to investigate its solution structures and vibrational energy transfer processes in pure dimethyl sulfoxide (DMSO) and in a DMSO/water mixture. A linear IR spectrum in the nitro-stretching mode region shows two major bands and one minor band in DMSO but changes to the two major bands mainly picture when adding water as an antisolvent of HMX, suggesting a transition from well-solvated and less perfect β-conformation to a less-solvated and close-to-perfect β-conformation. The latter bears a similar asymmetric nitro-stretch vibration profile to the β-polymorph in the crystal form. Density functional theory computations of the nitro-stretching vibrations suggest that HMX in DMSO may be in a NO2 group rotated β-conformation. Two-dimensional IR cross-peak intensity reveals intramolecular energy transfer between the axial and equatorial nitro-groups in the β-HMX on the ps time scale, which is slightly faster in the mixed solvent case. The importance of water as an antisolvent in influencing the equilibrium solvation structure, as well as the vibrational and orientational relaxation dynamics of HMX, is discussed.