The issue of competitive advantage is the actual topic in times of globalization and the global crisis. The existence of a competitive advantage in the territory affects significantly its development and success at the territory market. Research of the competitive advantage due to the nature of the territory as a product requires the multidisciplinary approach. While at the corporate and national level, the issue of competitive advantage is given considerable attention, at the regional level it has been not completely researched yet. The aim of the paper is to process the methodology of use and building competitive advantage at the regional level based on the definition of basic terms in the research area. The basic sources of the research are the secondary research of scientific and professional literary resources, the primary research realised by Delphi method among experts from different countries and a conducted primary research by the method of structured interviews with representatives of regional authorities, which aimed to identify the nature of competitive advantage and methods, how to use it in ensuring sustainable development of the region.