This chapter provides a radical interactionist perspective beyond essentialisms and inside-outside dualisms. First, Nietzsche’s notion of “will to power,” which represents an ontology of dynamic interrelatedness, is elaborated as a radical critique of the essentialist approach. This Nietzschean ontology provides fundamental building blocks for developing a radical anti-essentialist view of the human self, which is also employed later in the book to analyze and evaluate what is considered an “enhanced human.” Then, Peirce’s “list of categories” is discussed, which enables developing a more systematic and more detailed interactionist account of self and self-formation. Nietzsche and Peirce’s fundamental views complement and strengthen one another, laying the groundwork for developing a refined account of self-formation that recognizes that the self is formed through dynamic interactions with its changing social and material environment without rendering it a mere product of contingent environmental influences.