Introduction: Infant mortality rate (IMR) is an important reflection of the well-being of infants and their mothers in a community. Even though IMR has decreased substantially before the start of the 20th century, it has experienced a stagnation in its reduction in the last 10 years. Overall, no prior study has examined the determinants of IMR in Oman from both a country level and multi-factorial perspective. This study aims to examine the macroeconomic (ME), sociodemographic (SD), and health status and resources (HSR) effects on IMR, as well as how they may interact with each other. Methods: This was a retrospective time-series study aiming to gather yearly data for Oman spanning a period of 43 years; from 1980 to 2022. Partial least squares-Structural Equation Modelling (PLS-SEM) was utilized to develop the exploratory model of the determinants of IMR. Data was collected from several local and international sources, and numerous quality assurance procedures were performed on them to ensure their quality. Results: The final model of the research indicates that HSR determinants have a direct, but negative effect on IMR (β=-0.617, p<0.001). SD has a direct and positive effect on IMR (β= 0.447, p<0.001). ME exerts only an indirect effect on IMR, with an estimate of -0.854, at p<0.001. ME determinants also exert some direct influences on both HSR (β=0.722, p<0.001) and SD (β=-0.916, p<0.001) determinants. Conclusion: This study's findings indicated the critical role that the economy plays in improving the overall health of the population, and in reducing IMR particularly. Furthermore, this research's results shed light on the great role that some health intervention programs (such as the immunization program) have had on reducing IMR. Thus, strategies that help to sustain these programs ought to be continually funded. Finally, these findings indicate that an integrated policy that addresses socioeconomic, health related factors, as well the overall macroeconomic environment is necessary for the health and well-being of the children, and the population overall in Oman.