As city framework, the city spatial organization is a broader and more comprehensive concept than city spatial structure. In fact, the spatial structure tends only to the physical structure of the city, while spatial organization takes also into account the examination and identification of various functions, including economic, social, transportation functions. In addition, high-rise buildings – as phenomena that have flourished in the past decade in Hamedan and are still growing – have always got influenced by various factors and have affected various urban aspects such as spatial-physical, economic, social, environmental, and traffic dimensions. In fact, in addition to the effects of this issue on the physical structure of the city, they have brought about many changes in the spatial and functional organization of the city such that changes in the daily commuting to shopping centers, offices, etc. in the city are clearly observable. On the other hand, the previous studies have rarely addressed the effect of high-rise buildings on the spatial and functional organization of the city in major areas of business. Therefore, the purpose of this study was to analyze and evaluate the effects of high-rise buildings in the form of major modern central business districts on the spatial-functional organization of Hamedan city. This study was applied in terms of purpose and descriptive-analytical in terms of method. Moreover, in order to collect the required data, the documents related to urban development plans, field observations, interviews, and questionnaires were used. Then, to analyze the obtained data, the spatial-locative analysis models in GIS environment were adopted. The conceptual model of this study provided 8 indices for the analysis of the effects of modern high-rise CBDs on city spatial-functional organization, and each of them was analyzed spatially. The results of the analyses indicated that in the single-core spatial organization of Hamedan city, there is a high concentration on the central part of the city, but this concentrated area is expanding and new urban cores are emerging due to various factors. One of the reasons for the appearance of these new cores is business-office high-rise buildings. Another noteworthy finding of this study is that the majority of these newly emerging urban cores are growing along Buali-Jahannama road. Therefore, due to the changes in the spatial-functional structure of the city, paying more attention to urban infrastructures and flexible planning should be among the main priorities of the city management.