Abstract: Cryogenic propellant tanks undergo multiple mission phases—such as ground hold, ascent, orbital flight, coasting, settling, and re-entry—during which the gravitational acceleration can vary dramatically. The resulting changes in gravity have a strong influence on the thermal and thermodynamic behavior of the two-phase fluid inside the tank, which is critical for reliable design and operation of cryogenic storage systems. This work develops a comprehensive numerical model in Python to simulate heat transfer and thermodynamic processes within the tank under both constant and varying gravity conditions. The model incorporates the gas phase, liquid phase, and tank wall regions in a fully integrated framework and employs a Crank–Nicolson semi-implicit method to ensure numerical stability and accuracy. The simulation accurately reproduces experimental observations, with pressure prediction errors below 3% and thermal stratification deviations within 1%. Simulation results reveal that dynamic gravity variations substantially alter the tank’s thermal characteristics: Pressure growth slows under microgravity; as the gravitational acceleration approaches zero, the pressurization rate further diminishes, whereas once normal gravity is restored, the pressure rises rapidly. The gas and liquid regions experience pronounced temperature fluctuations during gravity transitions, showing slight decreases under hyper gravity and increases when normal gravity is restored, with the variations becoming more significant in the upper regions of the ullage. Under variable-gravity conditions, the convective heat transfer power between the liquid phase and the tank wall is higher than that of the vapor phase. During the transition from hypergravity to microgravity, the heat transfer power decreases significantly, and as the gravitational acceleration approaches zero, the minimum heat transfer power also approaches zero. During the recovery from microgravity to normal gravity, a transient sharp increase followed by a decrease in the vapor–liquid heat transfer power is observed. Moreover, the smaller the initial gravitational acceleration, the larger the fluctuation amplitude, which may be an important cause of pressure and temperature oscillations within the system.