The European Commission in 2008 in its working document Regions 2020: An Assessment of Future Challenges for EU regions identified challenges that EU regions might face in the coming years. First and foremost, these are the challenges of globalization, demographic change, climate change and the challenges associated with energy supply. On the basis of the report, we designed a system of factors and indicators which could be used to evaluate the vulnerability of regions to future development challenges. We tested this approach in the case of development regions in Slovenia. Results of the analysis show that the proposed approach is an appropriate professional basis for preparation of regional development programs.