The European Space Agency’s Genesis mission, scheduled for launch in 2028, is designed to enhance the Terrestrial Reference Frame (TRF). As a dynamic space observatory, Genesis will be equipped with instruments dedicated to the four space geodetic techniques. The mission is currently planned to operate in a near-polar orbit with an inclination of 95° and an altitude of approximately 6000 km, although an alternative orbital configuration with a reduced inclination of 60° is still under consideration. This simulation-based study investigates the influence of Genesis’ orbital inclination on the Very Long Baseline Interferometry (VLBI)-derived TRF, based exclusively on VLBI observations to the Genesis satellite. TRFs were determined for four different scenarios, comprising two orbital configurations (95° and 60° inclination) and two network setups: the existing VGOS network and an extended version including potential future stations. The results indicate that the estimated station coordinates are very similar for both the inclined and polar orbits, with no substantial difference in precision, which is quantified as the station coordinate repeatability in the East, North, and Up components. From a VLBI perspective, this suggests that either orbital configuration is suitable for TRF realization. While not directly tested in this study, the results suggest that optimized scheduling strategies, such as station-dependent scheduling of satellite observations, could improve the TRF determination.