The conquest of Constantinople by Mehmed II engendered transcultural exchanges and triggered competing projects for the renewal of the Roman Empire through the reuniting of Rome with Constantinople, the “New Rome.” These projects, promoted by successive popes of Rome and by the sultan of Constantinople-Istanbul, involved shifting alliances conjoining Christian and Muslim powers. The rhetoric of crusade and jihad formed the backdrop to Mehmed II’s elusive artistic conversations with Renaissance Italy, punctuated by moments of diplomacy and gift exchange with such city-states as Rimini, Naples, Florence, and Venice. It is against this background that this article reinterprets the sultan’s agency as a patron of Italianate art, arguing that he deliberately negotiated the expanding Western and Eastern horizons of his empire through visual cosmopolitanism and creative translation. The importation of foreign artistic idioms, along with the creation of an indigenous aesthetics of fusion, contributed to the construction of a multifaceted imperial identity. The cultivation of heterogeneous visual idioms—Ottoman, Timurid-Turkmen, Roman-Byzantine, and Italian Renaissance—resonated with the cultural pluralism of Constantinople, a site of encounter repopulated with a multiethnic and multiconfessional community to promote international trade and diplomacy. The epilogue traces the longevity of Mehmed II’s legacy throughout the sixteenth century.