Abstract Background Despite the high and increasing rates of cannabis and nicotine/tobacco product (NTP) use during pregnancy, the impact of their combined use on health outcomes in offspring remains poorly understood. Given the growing body of research on prenatal cannabis and NTP co-exposure and its effects on neonatal, behavioral, cognitive, and physiological outcomes in offspring, we conducted a systematic review to synthesize the existing literature and evaluate whether prenatal co-exposure results in additive and/or synergistic adverse effects compared to prenatal cannabis-only exposure and prenatal NTP-only exposure. Methods We searched Medline, Embase, and PsycINFO databases via OVID for human and animal studies examining the association...