Mortality rates from pulmonary embolism (PE) remain significant, highlighting the need for alternative treatment strategies beyond traditional anticoagulation. Percutaneous interventions, including mechanical thrombectomy and catheter-directed thrombolysis, are emerging as promising options. Given the complex pathophysiology and unique risk profiles of these patients, meticulous multidisciplinary planning is essential. Anesthesiologists play a central role in coordinating care and managing perioperative risks to improve outcomes. This article provides insights into best safety practices and shares experiences from a leading quaternary center. It offers guidance for anesthesia providers to proactively engage in comprehensive risk stratification, participate in multidisciplinary discussions, and support robust contingency planning for managing PE patients undergoing percutaneous interventions in non-operating room anesthesia settings.