Nanoparticles possess unique, size-driven properties. However, they can be challenging to use as they easily agglomerate - their high surface area-to-volume ratio induces strong interparticle forces, generating agglomerates that are difficult to break. This issue prevails in organic particles as well, such as cellulose nanocrystals (CNCs); when in their dried form, strong hydrogen bonding enhances agglomeration. Ultrasonication is widely applied to prepare CNC suspensions, but the methodology employed is non-standardized and typically under-reported, and process efficiency is unknown. This limits the ability to adapt dispersion protocols at industrial scales. Herein, numerical simulations are used in conjunction with validation experiments to define and optimize key parameters for ultrasonic dispersion of CNCs, allowing an operating window to be inferred.