This Element introduces the Existential-Spiritual Psychotherapy framework as a promising clinical and research tool and then integrates it with the three pillars of the Multicultural Orientation framework. Section 1 presents Existential-Spiritual Psychotherapy by exploring how spirituality and religion intersect with existentialism and how all three relate to psychotherapy, psychological symptoms, well-being, and flourishing. Section 2 details the Existential-Spiritual Narrative as a roadmap that offers a process framework and introduces the integration of dynamic and culturally sensitive symbols. Section 3 explores existential-spiritual comfort, encouraging therapists' self-awareness around spiritual themes. Section 4 identifies common existential-spiritual opportunities, helping clinicians recognize and engage culturally embedded spiritual content. Section 5 discusses existential-spiritual humility, promoting a posture of humble expertise when navigating spiritual material. Throughout, the authors offer an empirically informed, culturally attuned framework while promoting a dialectical balance in integrating spirituality and religion into psychotherapy.