This study attempts an in-depth comparative analysis of cultural entrepreneurship in two border islands of the North Aegean—Imbros and Lesvos—which fall under different state and cultural contexts, Turkey and Greece, respectively. The aim of the research is, on the one hand, to record the current situation of cultural entrepreneurship on the two islands and, on the other hand, to highlight the potential for its sustainable use as a tool for the strengthening of the local economy. The study is based on primary quantitative data collected through structured questionnaires addressed to local stakeholders, residents and professionals in the cultural and tourism sector on the two islands. The comparative analysis of the responses highlights the perceptions, attitudes and practices related to cultural entrepreneurship, the use of local cultural resources, the challenges faced by local communities, and their relation to the enhancement of local identity, social cohesion and sustainable regional development.