Background and aims: Breast and ovarian cancers affect the lives of many women worldwide. Female cancer survivors often experience hot flashes, a subjective sensation of heat associated with objective signs of cutaneous vasodilatation and a subsequent drop in core temperature. Breast and Ovarian cancer patients also suffer from sleep difficulties and mental health issues. The present study aimed to assess the effectiveness of Bubble, a novel artificial intelligence–virtual reality (AI–VR) intervention for the treatment of hot flashes in female breast or ovarian cancer patients. Methods: Forty-two women with breast and/or ovarian cancer participated in the study. The mean age was 47 years (range: 25–60 years). Patients suffered from hot flashes at different frequencies. They used Bubble, a virtual reality (VR) mobile psychological intervention based on elements from both cognitive behavioral therapy and mindfulness-based stress reduction. The intervention took place in a VR environment, in a winter wonderland setting called Frosty. Patients were instructed to use Bubble at home twice a day (morning and evening) and when experiencing a hot flash. Participants were asked to use the application for 24 consecutive days. Before and after this 24-day period, patients completed self-report questionnaires assessing hot flashes, general psychiatric distress, perceived stress, illness perception, sleep quality, and quality of life. Results: Between pre- and post-intervention, participants reported a significant reduction in the daily frequency of hot flashes, stress, general psychiatric distress, several domains of QOL, and sleep difficulties, as well as an improvement in illness perception. In addition, they reported very high satisfaction with Bubble. Importantly, both age and baseline levels of psychopathology moderated the effect of Bubble on sleep difficulties. Discussion: This study showed preliminary evidence for the potential of VR interventions in alleviating hot flashes and accompanying mental distress among those coping with breast and ovarian cancer. VR is a powerful therapeutic tool, able to address mind–body aspects in a direct, vivid way. More studies are needed in order to fully understand the potential of this unique intervention.