Indonesia strives for a renewable energy share of 23% by 2025. One option to contribute to this goal is Ocean Thermal Energy Conversion (OTEC). Despite a global theoretical potential of up to 30 TW, its economically deployable share remains unknown. This paper proposes a novel methodology, which enables to determine OTEC’s economic potential for any regional scope considering technical, economic and natural variables. The methodology was tested for 100 MWe OTEC in Indonesia on a provincial and national level. Against a regionally variable electricity tariff of 6.67–18.14 US$ct.(2018)/kWh, the national economic potential is 0–2 GWe with a Levelized Cost of Electricity (LCOE) as low as 15.6 US$ct.(2018)/kWh. With an annual electricity production of 0–16 TWh, OTEC could provide up to 6% of Indonesia’s electricity demand in 2018. The capacity factor, capital expenses and discount rate are the most sensitive variables of the LCOE on average. A nationally uniform feed-in tariff of 18 US$ct.(2018)/kWh or more could increase the economic potential significantly. The proposed methodology can be a helpful quick-scan tool for determining economically interesting OTEC sites for follow-up in-depth feasibility studies. Limitations are discussed and future research, amongst others upscaling scenarios with cost reducing effects like technological learning, is recommended.