Renewable energy resources and energy efficiency measures are effective means of curtailing CO2 emissions. Solar and wind technologies have been mostly developed to meet the energy demand of off-grid remote areas or locations without grid connections. However, it is well-known that the power generation of these resources is affected by daily fluctuations and seasonal variability. One way to mitigate such an effect is to incorporate hydrokinetic resources into the energy system, which has not been well investigated yet. Therefore, this study examines the prospects of designing a hybrid system that integrates hydrokinetic energy to electrify an off-grid area. Hydrokinetic energy generation depends on water flow velocity (WFV). We estimate WFV by a model-based approach with geographical and weather data as inputs. Together with the models of the other components (wind turbine, PV panel, battery, and diesel generator) in the micro-grid, an optimization problem is formulated with the total net present cost and the cost of energy as performance criteria. A genetic algorithm (GA) is used to solve this problem for determining an optimal system configuration. Applying our approach to a small community in Nigeria, our findings show that the flow velocity of a nearby river ranges between 0.017 and 5.12 m/s, with a mean velocity of 0.71 m/s. The resulting optimal micro-grid consists of 320 kW of PV, 120 units of 6.91 kWh batteries, 2 (27 kW) hydrokinetic turbines, an 120 kW converter, zero wind turbines, and a 100 kW diesel generator. As a result, the total energy generated will be 471,743 kWh/year, of which 12% emanates from hydrokinetic energy. The total net present cost, the cost of energy, and the capital cost are USD 1,103,668, 0.2841 USD/kWh, and USD 573,320, respectively.