A recent interest in implementing Nature-Based Solutions through Biophilic Design (BD) strategies has risen for the creation of comfortable indoor environments. Despite lab studies indicating benefits for work efficiency, the lack of preliminary design assessments has hindered their implementation. Virtual Reality (VR) has emerged as an effective tool for data collection in highly realistic environments, addressing such limitations. While current research on BD has mainly emphasized the visual connection with nature, it is important to note that individual experiences are multisensorial. This paper presents an innovative design approach for the preliminary assessment of BD strategies in VR. A case study compares three office layouts (Indoor Green – IG; Outdoor Green – OG; Non-Biophilic - NB) and three acoustic scenarios (Office – O; Office + Traffic – O + T; Office + Nature – O + N) with 198 participants performing cognitive tasks for each acoustic condition, alongside surveys. Results of sense of presence, immersivity (visual), sensory congruency (acoustic), and cybersickness disorders indicate the effectiveness of VR in the preliminary evaluation of BD interventions (ecological validity). The outcomes of the cognitive test highlight a positive influence of audio-visual connections with nature on working memory, inhibition, and task-switching performance. The most supportive visual*acoustic condition is identified as Natural sound in the IG setting, while O + T in the NB environment proves to be the most disruptive. The findings reveal a significant impact of the acoustic environment on the soundscape assessment: the O + N scenario enhances both pleasantness and eventfulness compared to the O scenario. An interaction between audio-visual stimuli was observed regarding pleasantness, with IG being more effective in the O + N scenario, and OG in the O + T scenario.