The territory of Beira Interior Norte in Portugal with the province of Salamanca in Spain have low demographic densities and populations in deep regression and aging as a result of migration movements, economic disarticulation, and specific context costs, given the different administrative framework and public policies. Promoting entrepreneurship in peripheral border regions is a key strategy for their sustainability, as part of the Europe 2020 goals for smart, sustainable, and inclusive growth. The chapter aims to provide guidelines for greater interaction between the results from the statistical analysis and its interpretation by local actors. In addition, indicate vectors that will help to design and develop the natural entrepreneurship dynamics for the Portugal/Spain border region, reinforce cooperation in the articulation of strategies, and the development of collaborative networks between entrepreneurs, training entities, business associations, and administrative entities have been explored.