This paper presents a comprehensive numerical investigation of the performance of pulsating heat pipes (PHPs) within nuclear reactor cooling systems. A volume of fluid (VOF) method was used to simulate the complex multiphase flow, providing detailed insights into fluid distribution, phase interactions, and temperature variations under different operating conditions. The simulations revealed distinct phase separation and convective flow patterns that enhance heat transfer efficiency, which is critical for optimizing thermal management in nuclear reactors. Additionally, artificial neural network (ANN) models were employed to predict volume fractions and wall temperatures, achieving high accuracy with R2 values of 0.99 and 0.98, respectively, and low mean absolute errors (MAE). The ANN models also reduced computational time by 90% compared to traditional numerical simulations. These findings highlight the potential of PHPs to improve heat transfer in nuclear systems and demonstrate the practicality of ANN models for real‐time thermal optimization. The research contributes to enhancing the safety and efficiency of nuclear reactor cooling systems, with broader implications for thermal management across various engineering applications.