The trilateral biosphere reserve in the Eastern Carpathians borders Poland, Slovakia and Ukraine and represents a key model for conserving biological diversity with respect to socio-economic and sustainable development. It is the regional representative of much diversity (language, history, culture, legal framework, and land use and management), and ecological studies are more accessible than data on the mutual effect of nature conservation on the local economy. Our study compares demography, land use, revenue of local stakeholders and the development of eco-tourism using data from the Slovakian and Ukrainian UNESCO World Heritage regions, where both Slovak and Ukrainian stakeholders profit mainly from the forestry industry, though additional but small incomes are derived from local recreation. Incomes from tourism are higher in Ukraine than in Slovakia, while in Slovakia significantly higher income comes in from local taxes than in Ukraine. These factors lead to depopulation (especially of young people) and marginalization of nature conservancy in the region. The forestry industry, with few and less sophisticated job opportunities, and a generally negative impact on the environment (intensive logging, soil erosion, etc.), casually suppresses the creation and development of eco-tourism essentials to the region. To mitigate this effect, this study suggests several steps toward the development of eco-tourism in the Eastern Carpathians–Poloniny region.