Designing and optimizing a bioreactor can be an especially challenging process. Computational modelling is an effective tool to investigate the effects of various operating parameters on bioreactor performance and identify the optimum ones. In this work, a computational fluid dynamics-population balance model (CFD-PBM) was developed to elucidate the effect of different geometrical and operating parameters on the hydrodynamics and mass transfer coefficient of a batch stirred tank bioreactor. The validated model was projected to predict the effect of different parameters including the gas flow rate, the impeller off-bottom clearance, the number of agitator blades, and rotational speed of the impeller on the velocity profiles, air volume fraction, bubble size distribution, and the local gas mass transfer coefficient (K
l
a) in the bioreactor. Air bubble breakup and coalescence phenomena were considered in all simulations. Factorial experimental design approach was employed to statistically investigate the impacts of the aforementioned operating and geometrical parameters on K
l
a and bubble size distribution in the bioreactor in order to determine the most significant parameters. This can give an essential insight into the most impactful factors when it comes to designing and scaling up a bioreactor.