This study presents a comprehensive three-dimensional Computational Fluid Dynamics (CFD) analysis of the pre-cooling process of a Type B LNG tank using various refrigerants, including liquid nitrogen (LN), nitrogen gas (NG), liquefied natural gas (LNG), boil-off gas (BOG), and their combinations. The simulation model accounts for phase change (through the mixture multiphase model), convective heat transfer, and conjugate heat exchange between the fluid and the tank structure. The results indicate that liquid nitrogen is the most efficient refrigerant, achieving the highest cooling rate through both latent and sensible heat. LNG also demonstrated a relatively high cooling rate, 79% of that of liquid nitrogen. Gas-only pre-cooling schemes relying solely on sensible heat exhibited slower cooling rates, with BOG achieved 79.4% of the cooling rate of NG. Mixed refrigerants such as NG + LN and BOG + LNG can achieve comparable, while slightly slower, cooling than the pure liquid refrigerants, outperforming gas-only strategies. A further assessment of the heat transfer coefficient suggests the mixed cooling schemes have almost identical heat transfer coefficient on the inner tank surface to the liquid cooling scheme, over 5% higher than the gas refrigerants. The study also highlighted the uneven temperature distribution within the tank due to the bulkhead’s blockage effect, which can induce significant thermal stress and potentially compromise structural integrity. Mixed schemes exhibit thermal gradients higher than those of gas schemes but lower than those of liquid schemes, while achieving cooling speeds comparable to liquid schemes if the inlet velocity of the refrigerants is properly configured. These findings offer valuable insights for developing safer and more efficient pre-cooling procedures for Type B LNG tanks and similar cryogenic storage tanks.