Abstract BACKGROUND Complex clinical decision-making in neuro-oncology is a multifaceted process involving numerous specialties influenced by various objective factors and patient preferences. Modeling these multidisciplinary neuro-oncology discussions presents significant challenges, particularly given the multimodal nature of the data. Recent advancements in large language models (LLMs) have enabled the development of LLM “agents”. These agents pave the way for multi-agent systems capable of simulating interacting components, thus capturing the nuances of interdisciplinary clinical discussions. MATERIAL AND METHODS Utilizing GPT-4, we developed conversational agents with an agent-based modeling (ABM) approach; each agent was assigned a specific specialty. We simulated their interactions in various clinical decision-making scenarios. Lastly, we simulated 30 patient-agents and included them in the ABM system. We applied this ABM approach to a dataset of 16 clinical vignettes extracted from the UCSF Clinical Data Warehouse of primary adult glioma patients who underwent tumor board (TB) reviews. The TB decision was used as ground truth for quantitative evaluation. Seven independent clinicians evaluated the final decisions. RESULTS Our quantitative assessment showed that, when blinded to whether ABM or TB generated responses, evaluators preferred ABM recommendations 47.8% of the time, followed by TB recommendations (38%). The highest recommendation concordance was between TB and ABM (50.6%). The ABM was deemed clinically accurate in 76.8% of cases and provided clinically appropriate reasoning in 73.2%. Our qualitative assessment showed that including the patient agent significantly influenced the course of discussions, notably when the patient agents participated in the system by stating their healthcare goals. The most recommended individual treatment was standard-of-care chemotherapy, followed by targeted therapies, clinical trials, immunotherapy, and palliative care. The least frequently recommended management options were radiation, surgery, consultation with other specialties, and devices. CONCLUSION This study underscores the potential of ABM in neuro-oncology, particularly in simulating complex, real-world scenarios. ABM not only empowers patients but also offers clinicians a novel tool for understanding and navigating the multifaceted landscape of patient preferences and treatment options. It provides a platform for clinicians to visualize the potential impacts of various decisions, enhancing their ability to provide personalized, effective care. We envision future work where ABM systems are patient-centric, enabling patients to explore the potential impacts of their individual characteristics on clinical management options.