This paper aims at addressing sustainability concerns in vulnerable insular territories. Such concerns are due to the rising overtourism phenomenon that affects islands at a rapidly escalating pace; and renders sustainable local development of these outstanding areas – from a natural and cultural viewpoint – at stake. Towards this end, this work capitalizes on current literature and attempts to structure a methodological framework and a respective set of indicators’ groups that are capable of assessing dimensions of overtourism in each single tourism destination, thus providing evidence-based and more robust guidelines for articulating policy decisions that can remedy incidents of overtourism. The proposed methodological framework follows a place-based approach and combines tourism demand and supply data with environmental, social, economic and spatial data and respective indicators for assessing tourism density and intensity of each destination’s tourism pattern and related multi-dimensional impacts. Validation of both the proposed framework and indicators’ groups is conducted in Santorini Island, Greece, i.e., an island that lies at top positions of many lists of destinations, marked as suffering by overtourism. Results show that Santorini Island is confronted with severe overtourism impacts, which are highly affecting its identity, productive model and spatial pattern, while endangering its natural and cultural wealth.