Cellulose nanocrystals (CNCs) are widely used in industrial applications due to their high strength, sustainability, and tunable surface chemistry. However, the presence of bound water in CNCs, particularly in chemically modified forms, remains a challenge for processing and application. In this study, we investigate the drying behavior and water retention of native and TEMPO-modified CNCs using a combination of hybrid Grand Canonical Monte Carlo (GCMC)/Molecular Dynamics (MD) simulations and experimental validation. Our simulations reveal that while native CNCs can be fully dehydrated under low-pressure, high-temperature conditions (≤ 0.04% water content at 1 mbar, 110°C), TEMPO-modified CNCs retain significantly more water (1–7 wt%, depending on pressure). The presence of charged carboxylate groups and their associated counterions enhances water retention through strong electrostatic interactions, making complete dehydration nearly impossible under typical drying conditions. Experimental drying studies of TEMPO-modified CNC foams confirm these findings, with excellent agreement between simulated and measured water content. These results highlight the necessity of considering residual bound water in modified CNCs for moisture-sensitive applications and suggest that similar behavior can be expected in other chemically charged cellulose materials.