Background: Over the last 2 decades, virtual reality technologies (VRTs) have been proposed as a way to enhance and improve smoking cessation therapy. Objective: This systematic review aims to evaluate and summarize the current knowledge on the application of VRT in various smoking cessation therapies, as well as to explore potential directions for future research and intervention development. Methods: A literature review of smoking interventions using VRT was conducted. Results: Not all intervention studies included an alternative therapy or a placebo condition against which the effectiveness of the intervention could be benchmarked, or a follow-up measure to ensure that the effects were lasting. Virtual reality (VR) cue exposure therapy was the most extensively studied intervention, but its effect on long-term smoking behavior was inconsistent. Behavioral therapies such as a VR approach-avoidance task or gamified interventions were less common but reported positive results. Notably, only 1 study combined Electronic Nicotine Delivery Devices with VRT. Conclusions: The inclusion of a behavioral component, as is done in the VR approach-avoidance task and gamified interventions, may be an interesting avenue for future research on smoking interventions. As Electronic Nicotine Delivery Devices are still the subject of much controversy, their potential to support smoking cessation remains unclear. For future research, behavioral or multicomponent interventions are promising avenues of exploration. Future studies should improve their validity by comparing their intervention group with at least 1 alternative or placebo control group, as well as incorporating follow-up measures.