Introduction: Pulmonary embolism (PE) results from a blood clot that causes a blockage to one of the pulmonary arteries in the lungs. This blockage can cause symptoms ranging from dyspnea and chest pain to more severe ones, such as signs of obstructive shock, respiratory failure, and cardiac arrest. Systemic thrombolysis (ST) has been found to effectively decrease the mortality risk of patients who are currently hemodynamically unstable due to PE but also comes with an increased risk for bleeding, such as intracranial hemorrhage. Therefore, catheter-directed thrombolysis (CDT) is used when ST fails or when contraindicated. CDT helps minimize exposure to thrombolytics because of having a localized directed infusion of the agent to lysis the clot. Due to the nature of this procedure, this could be explored if CDT is a more effective and safer choice than ST. Methods: A systematic literature review using Scopus, PubMed, and Medline is done to search for the effectiveness and safety of catheter-directed thrombolysis in contrast to systemic thrombolysis. Results: 49 articles were found through these three search engines. Seven articles were found to be relevant and reviewed to compare the safety and effectiveness of CDT to ST. Conclusion: This study concludes that CDT is more effective and safer than ST in treating submassive PE with hemodynamic compromise and massive PE. This conclusion was solely based on retrospective studies. Future randomized controlled trials should be done to support this study's inference and see if guidelines regarding the standard of care can be changed.