Purpose <p>Alleviating psychological distress in women with breast cancer undergoing treatment is a major worldwide issue. The growing use of new technologies in healthcare to support patients requires a more in-depth appraisal of the optimal methods for delivering these interventions. The present study aims to explore the clinical potential of a 360° video of local landscapes to reduce psychological distress of breast cancer patients receiving intravenous chemotherapy. We presented the same content in two different viewing conditions (immersive vs. non-immersive) in order to isolate the specific effect of immersive technology.</p> Methods <p>Using a non-randomized parallel design, 42 patients were allocated in two groups and watched the 11-min video during chemotherapy, either via a head-mounted display (<i>n</i> = 22, immersive group) or a tablet (<i>n</i> = 20, non-immersive group). Data were collected at three time points: 1&#xa0;week before treatment (T0, online pre-test), just before video exposure (T1), and immediately after video exposure (T2) during chemotherapy. Assessments included psychological distress (primary outcome) at T0 and T2. Secondary outcomes included relaxation at T1 and T2, nature connectedness at T0 and T2, sense of presence at T2, and cybersickness at T1 and T2.</p> Results <p>Results showed that the 360° video delivered via a head-mounted display significantly reduced psychological distress (p =.042), increased relaxation (p &lt;.0001), and enhanced all dimensions of presence (general presence, p =.0002; spatial presence, p =.004; involvement, p =.052; and experienced realism, p =.015) compared to the tablet modality. However, nature connectedness increased from pre- and post-assessment, regardless of the level of immersion (p =.039). Interestingly, the 360° video did not cause any cybersickness and even led to a significant decrease in related symptoms (p &lt;.001) across both modalities.</p> Conclusions <p>These preliminary findings suggest that immersive devices provide greater psychological benefits than non-immersive devices. The use of local natural content is an innovative approach compared to the generic environments commonly used. Future studies should further investigate the potential of using local landscapes to enhance therapeutic outcomes. Overall, this study indicates that exposure to 360° virtual nature may serve as an effective and safe supplementary intervention to provide psychological support for breast cancer patients undergoing oncological care.</p>