The paper examines differentiation business strategies in food production in Braničevo-Podunavlje region (Serbia). The research methodology includes survey research focused on the producers engaged in the production of value-added agricultural products, which have a greater potential for differentiation and branding. A range of survey indicators enable farmers and entrepreneurs of differentiated products to emphasize key success factors, detect barriers, and generate business ideas and innovations. Survey research was conducted in the period December 2018–January 2019, among 67 farmers, legal entities, and unincorporated enterprises−producers of high-quality niche food products in Braničevo–Podunavlje region. Results of the research indicated vegetable and fruit processing, beekeeping, and milk processing as sectors of the most promising value-added food products, including those that form the region’s basket of products. The study’s findings should contribute to the development of differentiated business models in the food sector and strengthening their role in smart regional development.