Engineering structures, such as bridges, highways, airport pavements, and offshore platforms, are constantly exposed to varying degrees of fatigue loading. The accumulation of fatigue loads can result in structural damage well before reaching their ultimate load capacity. Consequently, a comprehensive assessment of fatigue performance and service life prediction for these structures is paramount. This study focuses on a parametric investigation of the fatigue performance of reinforced concrete slabs under high cyclic fatigue loading, employing the nonlinear finite element method. The research scrutinizes the influences of load levels, concrete grades, and reinforcement ratios on several key parameters, including structural deflection, reinforcement stresses, cumulative damage, and natural frequency degradation. This study develops the three-dimensional finite element models based on experimental data, with rigorous verification of the model's accuracy. The findings emphasize the considerable impact of load levels, concrete grades, and reinforcement ratios on deflection, reinforcement stress, and cumulative damage in fatigued reinforced concrete slabs. Notably, the main form of structural fatigue damage is fatigue fracture of steel reinforcement, but high load levels, low concrete strength and reinforcement rates can cause concrete fatigue damage. Increasing concrete strength and reinforcement ratio can increase the initial natural frequency of the structure and slow down the fatigue degradation at the natural frequency. Additionally, the study proposes a practical life prediction equation for engineering designers. This equation offers valuable tools for predicting the fatigue life of reinforced concrete slabs, aiding in the design and maintenance of durable engineering structures.