The purpose of this study is to develop a tyrosine kinase inhibitor (TKI) tablet with pharmaceutical equivalence to a reference drug by optimizing shear force and tablet hardness in the wet granulation process using the Design of Experiments (DoE). Wet granulation is commonly used to enhance powder flowability, and optimizing shear force during this process is essential for maintaining consistent granule and tablet quality. Impeller and chopper speed, as well as granulation time, are key process variables known to significantly influence granule characteristics. Shear force is proportional to tip speed, which can predict changes in shear force during the process. Tip speed is calculated using the formula πND/t. In this study, the central composite design method, a type of response surface methodology, was used to evaluate the effects of process parameters on critical quality attributes (CQAs). The independent variables (X) were shear force and tablet hardness (7–15 kp), while the dependent variables (Y) were dissolution rate (10, 15, and 30 min) and disintegration time. The results showed that granules with relatively low shear force and tablets with intermediate hardness (~11 kp) exhibited the most similar dissolution profile and disintegration time to those of the reference drug. Ultimately, optimizing the manufacturing process using DoE is expected to improve the final product quality and contribute to reducing development costs.