This qualitative interview-based study examines metaphysical views of natural scientists (n = 35), focusing on the relationship of self to the universe. We use as a framework the idea of oneness, the view that the universe is fundamentally one thing. We examine how scientists situate their positions on religion and ultimate reality engaging with this concept. Our main research questions are: (1) How do natural scientists conceive of ultimate reality? What is their ontological picture of the world/universe? (2) How do natural scientists relate their spiritual, religious, and ethical outlook to their scientific topic(s) of study? Participants hold a sophisticated range of views that are influenced both by religious self-identification and disciplinary field. They regularly turn to philosophy and theology to guide their forays into ultimate reality, including philosophical and theological traditions such as Daoism, Buddhism, Calvinism, Eastern Orthodox Christianity, and ancient philosophy. We found that natural sciences and humanities do not compete, but are complementary when it comes to meaning-making.