The article considers the factors influencing regional development on the part of start-ups, shows a cognitive model of such impact, and gives an analysis of scenario modeling in the Samara Region. The research results are aimed at creating favorable conditions for ensuring the progressive development of a single region and the entire Russian economy. To implement the goal, studies were carried out in the form of an expert survey aimed at assessing the impact of start-ups on regional development. The study included methods of systemic analysis, economic statistics, methods of sociological expert survey, a method of statistical data analysis, a method of qualitative peer review, and a method of cognitive modeling. The article presents the results of scientific research aimed at identifying the mutual influence of the basic factors of regional development and start-ups as an important element of the socioeconomic system. The works of many scholars are devoted to the analysis and research of the problem of innovative entrepreneurship. They reveal the aspects of studying innovative entrepreneurship in the context of improving the effectiveness of innovative activity and motivating entrepreneurship. This study highlights the importance of start-ups for the formation and development of effective regional innovation systems and actualizes investigations related to identifying the main directions in the activities of the region's start-ups. A comparative analysis of the scenarios was carried out and the most effective of them were determined for the Samara Region. The presented research results can be transferred and reproduced in any constituent entity of the Russian Federation. The obtained cognitive models can be used as basic models to back up large administrative decision-making in the field of managing the regional infrastructure for supporting small and medium-sized businesses to improve its adaptability to changes in external and internal factors and to determine the trajectories of sustainable development. In addition, the obtained models can be applied in the field of fundamental research on the functioning and development of regional socioeconomic systems, as well as in applied research in modeling options for sustainable development of regional socioeconomic systems.