Successful regional development involves the establishment of a sustainable system between natural resources and economic and social challenges confronting the population of a particular area. There are numerous criteria that define these relationships, which can be expressed quantitatively and qualitatively. For a more reliable analysis concerning regional development, mathematical models have been developed based on their quantification and the analysis of multiple criteria to obtain alternative solutions in quantitative form, suitable for a more accurate assessment and ranking in accordance with the advantages and priority of application. This paper provides a model of the choice and quantification of factors that affect the development of the Toplica District, an area with considerable natural resources and a significant lag in its overall development. The objective of this investigation is to evaluate and rank the dominant factors that influence the development of the region under investigation in terms of natural factors (soil, water…), human factors (demographic, qualification, education…), economic factors (agriculture, tourism…), social factors (infrastructure, health…), and environmental factors (land, forest…). The methodology presented here can be used in a modified form for an analogous assessment of the development factors of any other region with similar natural and anthropogenic characteristics.