“NHSOS” is a multidisciplinary sustainability project that has been implemented in the islandic area of the Southeastern Aegean basin. Chalki (Halki) is a small island of about 500 citizens located in the climate-sensitive area of the Eastern Mediterranean. Focusing on Chalki Island, the project aims to reduce environmental degradation throughout three key pillars of “GReco” Island and Smart Specialization Strategy (S3) initiatives, namely waste management optimization, air quality monitoring, and carbon footprint mitigation. The project engages with authorities, the community, and tourism stakeholders in order to promote the circular economy and low emissions strategies. This study evaluates current and projected waste generation trends and outlines sustainable waste management strategies tailored to the island’s unique geographic and socioeconomic context. Air quality and meteorological recordings from sensors are used in order to investigate the concentration of air pollutants as well as the impact of meteorology and traffic activity on the variability of pollutant concentrations. All carbon emission sources are qualitatively characterized following Life Cycle Assessment (LCA) standards. Subsequently, sustainable interventions and energy autonomy solutions are outlined to reduce the island’s total carbon footprint. The ”NHSOS” project provides solutions for islandic sustainability in Mediterranean regional-based ecosystems, addressing the challenges of climate change, air pollution, and unsustainable resource use.