Given the dominance of scientism in the contemporary era, the relationship between the Qur’an as a religious text and science can be examined through scientific interpretation, which may be regarded as one aspect of religion’s contemporary relevance. However, despite the influence of metaphysical presuppositions on science within a post-positivist framework, their implications for scientific interpretation have not been sufficiently addressed. This study aims to highlight those implications through a descriptive-analytical method based on collecting and analyzing relevant research sources. The findings show that the penetration of metaphysical presuppositions into the theoretical layer of the empirical sciences, and their entanglement with that layer, have limited the scope of these sciences and, consequently, the scope of scientific interpretation of the Qur’an. Accordingly, Qur’anic verses may be divided into two categories: first, purely trans-empirical verses, which contain truths beyond the reach of science and therefore cannot be scientifically interpreted; second, empirical-trans-empirical verses, in which only the empirical layer can be understood, while interpretation of the trans-empirical layer remains impossible. In this regard, interpreting verses related to human phenomena is far more difficult than interpreting those related to natural phenomena, because the empirical and trans-empirical layers are more deeply intertwined in human phenomena. Therefore, the impact of metaphysical presuppositions on science confines scientific interpretation of the Qur’an to the empirically accessible layers of human and natural phenomena.