Drilling using twist drill is the most frequently used secondary machining for fiber-reinforced composite laminates and delamination is the most important concern during drilling. The drill design and drilling parameters associated with thrust distribution on the drilling-induced delamination are presented. The core-center drill has been found to be more advantageous than the core drill in reference and practice experiences. Response surface methodology (RSM) is a very practical, economical, and useful tool for the modeling and analysis of experimental results using polynomials as local approximations to the true input/output relationship. Due to the radial basis function network's (RBFN) fast learning speed, simple structure, local tuning, and global generalization power, researchers in the field of manufacturing engineering have been using RBFN in nonlinear manufacturing studies. The present paper compares these two techniques using various drilling parameters (diameter ratio, feed rate, and spindle speed) to predict the thrust force for a core-center drill in drilling composite materials. The obtained results indicated that RBFN is a practical and an effective way for the evaluation of drilling-induced thrust force.