Countries worldwide, especially Nordic countries, have proposed a forest-based bioeconomy to halt systemic risks, such as climate change, and to create socioeconomic welfare. Entrepreneurs operating in various business sectors and regions face several complex challenges in this regard. However, the challenges faced by forest-based micro-entrepreneurs have not been addressed across various regions using systems thinking. This comparative case study aimed to identify the environmental, social, and economic challenges faced by forest-based micro-entrepreneurs and the spatial features of these challenges—their scale, interactions, and prevalence—in two different regions in Finland: Lapland and South Karelia. These regions’ economies rely heavily on the recreational value of nature and on the large-scale pulp and paper industries, respectively. Semi-structured interviews were conducted with micro-entrepreneurs from various sectors, such as forestry, logging, tourism, and natural products. The data were analyzed using qualitative content analysis. The framework used enabled a deeper spatial understanding of the challenges experienced by forest-based micro-entrepreneurs. The micro-entrepreneurs in the two case regions had great similarities in terms of themes related to trust, workload, and labor shortage. This may hinder the implementation of new practices in regional forest-based bioeconomy development. Future quantitative studies could validate the identified challenges for further policy development.