Optimization of extrusion cooking effects on the proximate composition, anti-nutritional factors, mass flow rate, and torque, among other responses of Bambara groundnut-based flour blends, was the objective of this research. Bambara groundnut, pearl millet, malted sorghum, and banana flours were blended in the ratio of 50:20:20:10, respectively. Box-Behnken design of response surface methodology (RSM) was applied. Extrusion cooking reduced crude protein (20.01-17.19%), reduced the activities of oxalates, saponins, and trypsin inhibitors by 88.31%, 87.30%, and 82.35%, respectively, and increased carbohydrate content (57.48-68.82%). Barrel temperature had a strong increasing correlation (R2 = 0.9033) with mass flow rate, while net torque increased (78.15-81.26%) with decreasing screw speed (350-300 rpm). The RSM was successfully used to design, process, and develop prediction model equations for the manufacture of the Bambara groundnut-based breakfast cereal. Therefore, up to 50% Bambara groundnut is acceptable for a nutritionally improved breakfast cereal using extrusion cooking.