This study explores the effect of internal gas pressure (P) on closed-cell natural rubber (NR) foams. Three key factors are analyzed using a 3D model during uniaxial compression: (1) the initial gas pressure (P0 = 1, 2, and 3 atm) inside the cells, (2) different cell sizes (D = 0.1, 0.2, 0.3, and 0.4 mm in diameter), and (3) the presence of defects (holes in the cell walls) in terms of their sizes (d = 0.07 to 0.1 mm). The findings reveal a negative relationship between the initial gas pressure and the relative internal gas pressure (α = P/P0) and a direct correlation with stress during compression. For instance, a change from 1 to 3 atm of the initial internal gas pressure results in a 158% decrease in α with only a 3% increase in stress. Larger cell sizes contribute to higher α but lower stress levels during compression. Changing the cell size from 0.1 to 0.4 mm generates a 27% increase in α but a 45% drop in stress. An analysis of hole sizes (cell connection) indicates that larger holes result in higher relative internal gas pressure, while smaller holes lead to higher stress levels because of more flow restriction. For example, increasing the hole size from 0.07 to 0.1 mm leads to an 8% higher α but a 32% stress reduction. These findings highlight the significant effect of the internal gas pressure inside the cells in determining the mechanical properties of rubber foams, which are generally neglected. The results also provide useful insights for better material design and different industrial applications. This study also generates predictive models to understand the relationships between stress, strain, initial gas pressure, cell size, and defects (holes/connections), enabling the production of tailor-made rubber foams by controlling their mechanical behavior.