Islands face unique challenges on their journey towards achieving carbon neutrality by the mid-century, due to the lack of energy interconnections, limited domestic energy resources, extensive fossil fuel dependence, and high load variance requiring new technologies to balance demand and supply. At the same time, these challenges can be turned into a great opportunity for economic growth and the creation of jobs with non-interconnected islands having the potential to become transition frontrunners by adopting sustainable technologies and implementing innovative solutions. This paper uses an advanced energy–economy system modeling tool (IntE3-ISL) accompanied by plausible decarbonization scenarios to assess the medium- and long-term impacts of energy transition on the energy system, emissions, economy, and society of the island of Mayotte. The model-based analysis adequately captures the specificities of Mayotte and examines the complexity, challenges, and opportunities to decarbonize the island’s non-interconnected energy system. The energy transition necessitates the adoption of ambitious climate policy measures and the extensive deployment of low- and zero-carbon technologies both in the demand and supply sides of the energy system, accounting for the unique characteristics of each individual sector, while sectoral integration is also important. To reduce emissions from hard-to-abate sectors, such as transportation and industry, the measures and technologies can include the installation and use of highly efficient equipment, the electrification of end uses (such as the widespread adoption of electric vehicles), the large roll-out of renewable energy sources, as well as the production and use of green hydrogen and synthetic fuels.