Tommaso Cornelio has much contributed to the renovation of Neapolitan Culture in XVII Century, mostly by spreading the knowledge of Descartes’ works, method and philosophical approach. His works, especially Progymnasmata physica (1663), became soon renown in the transalpine cartesian circles, notably by Malebranche. Cornelio’s work was vast and wide-ranging. Aware that the Cartesian program involved a radical reorganization of the entire field of knowledge, he was particularly sensitive to the new Cartesian anthropology and the interpretation of the human body in a mechanistic framework strictly ruled by the laws of Nature established by God. At the same time, Cornelius observes and explains the world of life and physiological processes within a broader horizon, examining, always critically, different philosophical-scientific traditions, from the pre-Socratics up to Renaissance thinkers (Telesio, Bruno, Campanella) and to his contemporaries (Bacon, Galileo, Harvey, Hobbes, Malphighi, Redi, and so on). We thus aim to show how the Cosentine philosopher and physician felt the need to situate the novelty of Cartesianism within a broader spectrum of ideas and experiences, and that it was in this wider framing that he evaluated and applied Descartes’ tools and ideas to specific subject matter. This wider framework allowed him to chart his own course within the new map of the physical world drawn by the French thinker.