The article assesses the natural conditions for the development of entrepreneurship, which is the basic determinant of the multifunctional development of a given territory. Achieving the objective formulated in this way, the answers to the following questions were sought: how do natural conditions, especially those considered valuable in terms of nature, affect the development of entrepreneurship – the dynamics and the structure of enterprises; do they favour diversification of economic entities and multifunctional development; how does the development of entrepreneurship translate into the use of endogenous resources of a given territory, into social processes (migration, unemployment, average wages)? The research (2012-2017) covered the region of Podkarpacie, with particular emphasis on counties with the highest and lowest share of natural value areas. The delimitation of counties was performed with the use of the complete linkage method, which allows one to distinguish subsets characterized by high internal similarity due to the adopted features. The research showed that natural values did not constitute an asset for the multifunctional development of these areas. This concerns both the development of the SME sector (the dynamics of the sector is lower than in the whole region and the compared group of counties) and the use of environmental values for the development of organic production - a clear decrease in the number of farms and the area of organic crops. The consequence of this is limited use of endogenous potential – high unemployment and high migration. This demonstrates the low effectiveness of cohesion policy and carries a high risk of depopulation of these areas, with all the complexity of such a process.