Thermo-hydraulic characteristics of supercritical CO2 (SCO2) flows in horizontal tubes with half-wall heat-flux conditions are investigated numerically, which is a common practice such as applications in solar parabolic trough collectors, while the heat transfer performance and the underlying mechanisms have not been fully understood. In heated flows, buoyancy acts to inhibit heat transfer when the top half of the tube wall is heated, however, when the bottom half of the tube wall is heated, this inhibition is alleviated, and the synergy between the temperature gradient and velocity fields improves thanks to the secondary flow in the near-wall region at the bottom wall. As a result, the heat transfer coefficient is ∼95% higher (on average) than in the case when the top half of the tube wall is heated. When the bottom half of the tube wall is cooled, buoyancy is expected to enhance heat transfer, while the synergy between the temperature gradient and velocity fields is supressed by the secondary flow in the near-wall region at the bottom of the tube. Conversely, when the top half of the tube wall is cooled, the buoyancy effect inhibits heat transfer, while the synergy between the temperature gradient and velocity fields is improved by the secondary flow in the near-wall region at the top of the tube, which eventually leads to an increase of ∼21% (on average) in the heat transfer coefficient relative to the case when the bottom half of the tube wall is cooled. Finally, the heat transfer discrepancy due to different heat flux conditions revealed in this study are employed in a heat exchanger model, indicating that the thermal performance of this device can be increased by ∼6% through an appropriate arrangement of the hot and cold flows without additional costs.