The physical environment of an alternate care facility (ACF) spans safety, security, infection prevention, emergency management, hazardous materials, and fire and life safety, and it proved inseparable from patient safety, staff wellbeing, and operational continuity. Symposium participants summarized operational lessons from establishing and sustaining ACFs across convention centers, hotels, tents, and other non-traditional spaces. Participants reported that effective sites integrated clinical staff into security and de-escalation rather than relying on law enforcement alone, controlled access through single monitored entrances, and managed both the internal care space and the external perimeter as part of patient care. Multidisciplinary walkthroughs were essential to identifying physical hazards before activation. Persistent challenges included the absence of smoke compartments in open and temporary structures, unverified ventilation and negative-pressure performance, unreliable power and connectivity, and environments lacking day-night differentiation that contributed to patient delirium. Recommended best practices include engineering environmental controls in advance, embedding infection prevention, wellness, and safety functions from activation, and protecting staff through dedicated respite and decompression space.