This paper seeks to explore the way Giovanni Pico della Mirandola treated the Orphics and the Pythagoreans in his Conclusiones nongentae, his early and most ambitious work, so that he formulates his own philosophy. I do not intend to present and analyze the sum of Pico’s references to Orphics and Pythagoreans, since such an attempt is beyond the scope of this paper. Rather, I aim to highlight certain Pico’s aphorisms that allow readers to understand and evaluate his syncretic method and his goals. In addition, I attempt to trace Pico’s sources and evaluate his proper knowledge, understanding and treatment of the Orphics and the Pythagoreans. Pico resorts to the Orphics and the Pythagoreans because he wants to give a practical and applied dimension to his philosophy. He attempted the revival of the original wisdom that underlies the traditions he combined. He was not a fan of the Aristotelian θεωρίης ἢνεκεν. Philosophy does not aim at proper knowledge, but is the key for the manipulation of the cosmos, physically and metaphysically speaking. Pico probably thinks of himself as the modern Orpheus: he does not intend to reveal the paths which cross the sensible and the intelligible, but he aspires to tread them.