The Gospel of John (3:3-5) reports an intriguing conversation between Jesus and the Pharisee, Nicodemus: Jesus replied, “Very truly, I tell you, no one can see the kingdom of God unless they are born again.” “How can someone be born when they are old?” Nicodemus asked. “Surely they cannot enter a second time into their mother’s womb to be born!” Jesus answered, “Very truly I tell you, no one can enter the kingdom of God unless they are born of water and the Spirit.” The Fatimid savant Jaʿfar ibn Manṣūr al-Yaman (d. ca. 346/957) alludes directly to this exchange in his Taʾwīl al-zakāt and writes of the second birth as “establishing knowledge of reality and spreading wisdom.” His engagement with pre-Islamic scriptures and efforts to adduce their spiritual meaning remained hallmarks of the Shiʿi Fatimid luminaries who followed him. Kirmānī (d. after 411/1020), for example, quoted directly from the Torah in Hebrew and the Gospels in Syriac, including this very verse. He connected being born again with being elevated from the blind conformism of sacramental worship (al-ʿibādah al-ʿamaliyyah) to the gnostic understanding of sapiential worship (al-ʿibādah al-ʿilmiyyah). Similarly, the Quran (23:12-14) speaks of seven stages of birth, culminating in “another creation.” Fatimid interpretations of the “second creation” echoed their understandings of the “second birth.” Intimately connected with these was the idea of swearing a first covenant (ʿahd), to the exoteric message of Prophet Muḥammad and a second covenant to the esoteric interpretation of his successors, the Imams. Using methods adapted from literary analysis and comparative religions, this paper will analyze the esoteric interpretation of birth and being born again in the writings of Fatimid authors, including the two aforementioned figures, Qāḍī al-Nuʿmān (d. 363/974) in his Taʾwīl daʿāʾim al-Islām, al-Muʾayyad Shīrāzī (d. 470/1078) in his Majālis, and Nāṣir-i Khusraw (d. after 462/1070) in his Wajh-i Dīn. In so doing, I will bring them into conversation with Christian commentators on being born again, such as Tertullian (d. 220 CE), Cyril of Jerusalem (fl. 350 CE), and St. John Chrysostom (d. 407). I will argue that the Fatimids, not unlike these Christian thinkers, harnessed the possibilities of esoteric interpretation (taʾwīl) to unveil multiple layers of meaning in scripture, touching on human psychology, the great chain of being, sacred history, and the evolution from sacrament to sapience. Such an endeavor opens pathways for conversations between the world’s two largest religious communities.