A continuous multistage mixed suspension, mixed product removal (MSMPR) cascade crystallization system has been modeled and optimized for both the steady-state and the startup behaviors when both cooling and antisolvent addition are applied as the crystallization driving forces. The optimal steady-state operating profiles of MSMPR cascade crystallizers have been obtained and found to be similar to the optimal batch trajectory. In addition, the minimum startup duration time is used as the objective function to optimize the startup behavior. Methods, including changing the initial solution compositions, applying dynamic antisolvent profiles, applying dynamic temperature profiles, and applying dynamic combined antisolvent and temperature profiles, are discussed and used to formulate the optimization problems. The optimal results indicate that for a cascade of two MSMPR crystallizers, it is possible to achieve a reduction of approximately 50% of the startup duration time and amount of waste. A model-free or direct design approach via closed-loop control to improve the startup performance is also proposed.