This paper presents the optimized approximation of finite element modeling for a complex tool holder spindle using both DOE (Design of Experiment) with Optimal Latin Hypercube (OLH) method and approximation modeling method with Radial Basis Function (RBF) neural network structure. The complex tool holder is used for holding a (milling/drilling) tool of a machine tool. The engineering problem of complex tool holder results from the twisting of spindle of tool holder. For this purpose, we present the optimized approximation of finite element modeling for a complex tool holder spindle using both DOE (Design of Experiment) with Optimal Latin Hypercube (OLH) method (specifically a module of $iSight^{(R)}$ FD-3.1) and approximation modeling method with Radial Basis Function (RBF) (another module of $iSight^{(R)}$ FD-3.1) neural network structure