Tabletop exercises offer a structured opportunity to assess strengths and potential gaps in preparedness and response plans in a safe learning environment. The New York City Health + Hospitals System-Wide Special Pathogens Program conducted an innovative and multidisciplinary tabletop exercise involving escalating scenarios of highly pathogenic avian influenza (HPAI) H5N1 in 2023. The goals were to assess patient screening processes for infectious diseases within healthcare facilities, infection prevention and control strategies, risk communication, and notification and involvement of public health stakeholders. Participants reflected on previous outbreak responses, discussed the importance of risk communication, and shared insights on tools and resources that would better support healthcare professionals in identifying and managing patients with HPAI/H5N1 infection. Key takeaways included establishing clear protocols for HPAI/H5N1 management, providing timely education to healthcare professionals, and assessing useful communication modalities. Methods: The exercise included escalating scenarios involving a single case of HPAI/H5N1 advancing to community transmission. Key participants spanned clinical departments, infection prevention and control, emergency management, and local public health stakeholders. Structured discussions targeted triggers for escalation, infection prevention strategies, and communication pathways. Results: Findings highlighted the need for tailored screening criteria, robust infection prevention protocols, clear communication strategies, and collaboration with public health authorities. Specific improvements included refining triage and isolation protocols, enhancing staff education, and leveraging syndromic surveillance systems. Conclusion: This exercise underscored the importance of proactive planning, multidisciplinary collaboration, and integration of biosafety measures to strengthen healthcare system resilience against HPAI/H5N1.