This study examines and analyzes the epistemological foundations and methodological framework of Ayatollah Muhammad Asif Mohseni (d. 2019), a prominent contemporary Islamic scholar, in his approach to the scientific exegesis of the Quran. Despite his distinguished contributions to the fields of hadith and rijāl (biographical evaluation of narrators), his approach to the interaction between the Quran and empirical sciences—one of the most significant yet challenging areas of contemporary epistemology—has not yet been subject to comprehensive and independent scrutiny. The primary objective of this article is to elucidate Ayatollah Mohseni’s epistemological and methodological framework and to reconstruct his interpretive model as a balanced approach to leveraging modern scientific advancements in understanding the Quran. Employing a descriptive-analytical approach and based on a content analysis of Ayatollah Mohseni’s written works, this study demonstrates that his interpretive methodology is grounded in clear and precise principles: conditional acceptance of a shared epistemic domain between the Quran and science with the ultimate goal of “guidance,” belief in the compatibility of the Quran with “definitive scientific knowledge,” adherence to the apparent meaning of the text while avoiding unwarranted reinterpretations, and, most crucially, an emphasis on a rigorous epistemological criterion distinguishing between “definitive and observable scientific findings” and “inferential and non-definitive theories.” An analysis of the application of these principles to specific Quranic verses—such as those concerning gravity, the movement of the Earth, and animal consciousness—reveals that Ayatollah Mohseni, while avoiding hasty correlations, judiciously utilized scientific insights to uncover deeper semantic layers of the Quran, thereby affirming its dynamism and timelessness in the contemporary world. The findings of this study present Ayatollah Mohseni’s interpretive model as a balanced, rationally grounded, and cautious approach, offering an effective framework for interdisciplinary studies of the Quran and science.