This study estimates the environmental and technical energy potential of the thermohaline conditions in the Mexico–Belize riverine estuary. Site-specific conditions were considered based on monthly water temperature, salinity, and river discharge field measurements along the Hondo River estuary from 2018 to 2019. The practical extractable energy assessment described the possibility of outlining a hypothetical ∼3 MW salinity gradient energy (SGE) plant, which could support 5.4–15.1% of houses in the main urbanised area. Low-income housing benefits can be viable for up to 7700 houses with either mechanical or natural ventilation under tropical weather conditions. Alternatively, this energy may be directed towards commercial shared zones between Mexico and Belize. SGE harnessing might be possible throughout the year with limited zero extraction periods provided by seasonal thermohaline variations in the estuary during the dry season and at mid-summer droughts. The energy potential of the Hondo River was compared with manatee presence to explore possible environmental implications from SGE harnessing. The periods of high energy potential were followed by peaks in manatee sightings with a 1–2-month delay. The SGE approach based on a small-scale energy-generation scheme for the local coastal urbanised area considering the binational framework is discussed.