Abstract: The helium-xenon (He-Xe) gas mixture exhibits excellent heat transfer performance at specific ratios, low fast neutron absorption cross-section, and good compressibility, making it suitable as a coolant for gas-cooled fast reactors (GFR) and as a working fluid for closed Brayton cycle systems. Rectangular narrow slit channels are widely present within the reactor core. These channels, formed by assembly tolerances, thermal expansion, and irradiation-induced deformation, create pathways for bypass flow. Accurately predicting the thermal-hydraulic behavior within these gaps is therefore crucial for determining core flow distribution and ensuring overall reactor safety. The flow and heat transfer characteristics of the He-Xe gas mixtures in these channels directly affect the reactor’s thermal-hydraulic behavior and system safety characteristics. The computational fluid dynamics (CFD) was employed to analyze the flow and heat transfer behavior of He-Xe gas in rectangular narrow slit channels in this study. The simulations were conducted using the SST k-ω turbulence model, and the standard turbulent Prandtl number (Pr_t) model was corrected using the Weigand-Kays model to accurately capture the heat transfer characteristics of the low-Prandtl-number mixture. The numerical methodology was validated against established experimental data, demonstrating strong predictive accuracy. A comprehensive parametric study was performed, investigating a range of molar masses, aspect ratios, mass flow rates, and heat fluxes. Using the thermal-hydraulic performance ratio (THPR) as the evaluation metric, the effects of thermal and geometric parameters, such as heating methods, aspect ratios, and surface roughness, were analyzed. Results show that the local Nusselt number under double-sided and single-sided heating exhibits similar values and trends. Heat transfer performance is slightly higher with bottom-side heating than top-side heating, especially under high heat flux. Single-sided heating results in lower peak wall temperatures compared to double-sided heating, allowing higher heat flux tolerance. This indicates that single-sided heating conditions can provide a greater safety margin. The study also reveals hot spots in the channel corners, which are effectively mitigated by increasing the mass flow rate. This enhancement is attributed to the thinning of the thermal boundary layer and increases near-wall turbulence. The Dittus-Boelter correlation significantly overestimates the Nusselt number, particularly at high Reynolds numbers, with deviations exceeding 10%, while friction factors are generally 15% lower than predicted by the Blasius equation. System pressure has negligible effects on flow and heat transfer. Higher xenon fractions reduce overall heat transfer performance. This finding is critical for long-term operation, as potential helium leakage could lead to a gradual increase in xenon fraction, thereby degrading the core’s heat removal capability over time. Larger aspect ratios increase friction factors and decrease THPR. Surface roughness enhances heat transfer but slightly increases flow resistance, with limited overall impact.