We introduce a new architecture of hetero-hybridized feed-forward neural networks composed of fuzzy set-based polynomial neural networks (FSPNN) and polynomial neural networks (PNN) that are based on a genetically optimized multi-layer perceptron and develop their comprehensive design methodology involving mechanisms of genetic optimization and Information Granulation. The construction of Information Granulation based HFSPNN (IG-HFSPNN) exploits fundamental technologies of Computational Intelligence(CI), namely fuzzy sets, neural networks, and genetic algorithms(GAs) and Information Granulation. The architecture of the resulting genetically optimized Information Granulation based HFSPNN (namely IG-gHFSPNN) results from a synergistic usage of the hybrid system generated by combining new fuzzy set based polynomial neurons (FPNs)-based Fuzzy Neural Networks(FNN) with polynomial neurons (PNs)-based Polynomial Neural Networks(PNN). The design of the conventional genetically optimized HFPNN exploits the extended Group Method of Data Handling(GMDH) with some essential parameters of the network being tuned by using Genetic Algorithms throughout the overall development process. However, the new proposed IG-HFSPNN adopts a new method called as Information Granulation to deal with Information Granules which are included in the real system, and a new type of fuzzy polynomial neuron called as fuzzy set based polynomial neuron. The performance of the IG-gHFPNN is quantified through experimentation.