Although knowledge on spiritual care provision in an interfaith context is essential for addressing the diversity of patients’ religious and spiritual needs, an overview of the literature is lacking. Therefore, this article reviews the empirical literature on interfaith spiritual care (ISC) in professional caring relationships. A systematic search in electronic databases was conducted to identify empirical studies published after 2000. Twenty-two studies were included. The quality of the included studies was assessed, and their results were thematically analyzed. The majority were conducted in North America, mainly using qualitative methods and focusing on professional caregivers, who had a variety of professional and spiritual backgrounds. Two core categories were identified: (1) normativity: reasons for (not) wanting to provide ISC, in which universalist and particularist approaches were identified; and (2) capacity: reasons for (not) being able to provide ISC, which included the competences that health care professionals may need when providing ISC, as well as contextual possibilities and restraints. This systematic review identifies gaps in the literature and indicates that future studies have to explore patient perspectives on ISC.