The dichotomy between science and religion, rooted in Western secularism, has generated an epistemological crisis characterized by the erosion of ethical values, moral responsibility, and spiritual purpose in the development of modern science. This study examines a holistic approach to scientific paradigms through the reconstruction of the integration of science and Islam in the contemporary era. Employing a qualitative library research method, the study analyzes the intellectual contributions of prominent scholars of knowledge integration, including Syed Muhammad Naquib al-Attas, Ismail Raji al-Faruqi, and Seyyed Hossein Nasr, while also reviewing recent academic literature on the Islamization of knowledge and Tawhidic epistemology. The findings indicate that the reconstruction of an integrated science–Islam paradigm can be developed through three fundamental pillars: a Tawhid-based ontological foundation, an epistemological framework that synthesizes revelation and reason as complementary sources of knowledge, and an axiological orientation that directs scientific inquiry toward human well-being and social benefit. This holistic approach goes beyond the mere incorporation of religious content into science education; rather, it entails a paradigmatic transformation that situates scientific knowledge within a framework of divine values and higher purposes. The study concludes that the harmonization of science and religion offers a viable response to the contemporary crisis of values, including environmental degradation and the dehumanizing effects of technological advancement. Furthermore, it contributes to the formation of scientists and scholars who possess not only intellectual excellence but also moral and spiritual integrity.