In this paper, we introduce a new topology of Radial Basis Function-based Polynomial Neural Networks (RPNN) that is based on a genetically optimized multi-layer perceptron with Radial Polynomial Neurons (RPNs). This study offers a comprehensive design methodology involving mechanisms of optimization algorithms, especially Fuzzy C-Means (FCM) clustering method and Particle Swarm Optimization (PSO) algorithms. In contrast to the typical architectures encountered in Polynomial Neural Networks (PNNs), our main objective is to develop a design strategy of RPNNs as follows : (a) The architecture of the proposed network consists of Radial Polynomial Neurons (RPNs). In here, the RPN is fully reflective of the structure encountered in numeric data which are granulated with the aid of Fuzzy C-Means (FCM) clustering method. The RPN dwells on the concepts of a collection of radial basis function and the function-based nonlinear (polynomial) processing. (b) The PSO-based design procedure being applied at each layer of RPNN leads to the selection of preferred nodes of the network (RPNs) whose local characteristics (such as the number of input variables, a collection of the specific subset of input variables, the order of the polynomial, and the number of clusters as well as a fuzzification coefficient in the FCM clustering) can be easily adjusted. The performance of the RPNN is quantified through the experimentation where we use a number of modeling benchmarks - NOx emission process data of gas turbine power plant and learning machine data(Automobile Miles Per Gallon Data) already experimented with in fuzzy or neurofuzzy modeling. A comparative analysis reveals that the proposed RPNN exhibits higher accuracy and superb predictive capability in comparison to some previous models available in the literature.