This section is organized as a conceptual roadmap to demonstrate the applicability of a substance-unconscious for a contemporary diagnosis. It begins with Gilles Deleuze and Felix Guattari’s ideas of the plane of consistency and becoming-animal, connecting through Friedrich Nietzsche’s unhistorical man and horizonality to Franco ‘Bifo’ Berardi’s caution of a third unconscious arising out of the post-coronavirus crisis, which is encapsulated by Catherine Malabou’s idea of destructive plasticity that underscores the depressive and depersonalized states of the body when the mind is in distress. To conclude, I will speculate what could arise as the third unconscious. Each concept carries forward, implicitly or explicitly, Spinoza’s insistence of the body and affect, and the importance of creation with regard to the unconscious, and each philosopher offers a stepping-stone to a larger and integrated understanding of how we can conceptualize a substance-unconscious.