This study gives a new methodological framework regarding the measuring of the contribution of some key-factors on the regional growth rate and forecasting the future development rates, based on Neural Network Models (NN Models). It’s a serious attempt to study the contribution of twelve key-factors to the change of the Regional Gross Domestic Product of the Region of East Macedonia -Thrace during a long-term of growth process, by creating and using a suitable Neural Network Model. Specifically, twelve key-factors, time functioned in the period 1991-2008, are studied for the first time, in order to be investigated, scientifically, firstly their % contribution to growth of the regional economy and secondly, to be predicted how much the (Regional Growth Domestic Product) RGDP-under certain conditions-will be changed. It’s a NN Model with inputs the twelve key-factors in order to be evaluated and measured, at the best precise, their percentage contribution to the RGDP. The model and results can be found further into the article.