The dehydration of nitrofurantoin monohydrate II was monitored under different isothermal conditions (100, 105, 110, 115, and 120 °C) using Raman spectroscopy in the low- (-300 to 15 and 15 to 300 cm^-1) and mid- (300 to 1800 cm^-1) frequency regions. Clear and subtle spectral differences were observed for Raman spectra in the respective domains for solid-state transformations. Multivariate curve resolution was used to extract the information on the solid-state forms present and their relative abundances during the isothermal dehydration experiments. Theoretical modeling of nitrofurantoin hydrates (nitrofurantoin monohydrates I and II) and anhydrous forms (α and β) was carried out using density functional theory with periodic boundary conditions to support the interpretation of low-energy vibrational modes. Midfrequency Raman spectroscopy detected the onset of the dehydration process (where observed) of nitrofurantoin monohydrate II ∼100-300 s before the low-frequency Raman spectral domain depending on the isothermal condition. This was attributed to the change of order during the process, where disruption of localized molecular arrangements within the monohydrate crystal structure is first expected to occur.