Non-operating room anesthesia (NORA) has grown rapidly in recent decades, now representing more than half of anesthetics delivered in the United States. This expansion reflects the rise of minimally invasive interventions, widespread use of advanced imaging, and increasing demand for outpatient procedures such as gastrointestinal endoscopy. NORA encompasses diverse sites—including endoscopy suites, cardiac catheterization and electrophysiology labs, interventional radiology, and magnetic resonance imaging (MRI)/computed tomography scanners—that present unique logistical, technical, and safety challenges compared to traditional operating rooms (ORs). Unlike the OR, many NORA locations are geographically remote, poorly designed for anesthetic workflows, and supported by staff with limited anesthesia training. Ergonomic constraints restrict access to the patient and airway, especially in prone or confined positions, and monitoring may be limited or require specialized equipment (e.g., MRI-compatible devices). Patients presenting for NORA often carry a high burden of comorbidities, such as advanced heart failure, cirrhosis, or malignancy, further compounding procedural risks. Despite these challenges, adherence to the same standards of monitoring, crisis preparation, and communication used in the OR enables safe NORA delivery. Pre-procedural checklists, simulation training, and collaboration with proceduralists are essential safeguards. Internists play a vital role in optimizing these patients before procedures and co-managing complications afterward. Awareness of NORA environments enhances internists’ ability to anticipate risks, counsel patients, and coordinate with anesthesiologists, thereby improving perioperative safety and outcomes.