Background: The routine incorporation of aerosol therapy in the daily responsibilities of intensive care unit (ICU) nurses, specifically in the management of patients undergoing invasive mechanical ventilation (MV), is an established practice. However, the depth of understanding regarding the clinical practices of ICU nurses in aerosol therapy remains inadequately explored. Limited studies have specifically addressed the nuanced comprehension and application of atomization safety protocols by ICU nurses during the administration of aerosol therapy to patients undergoing invasive MV. Aim of the Study: This study aimed to assess nurses' role regarding nebulization therapy for patients with mechanical ventilation in emergency care unit. Subjects and Methods: Research Design: A descriptive design was carried out in this study. Study Setting: The study conducted within the surgical intensive care units of Zagazig University Hospitals in Sharkia Governorate, Egypt. Subjects: A carefully chosen sample of 30 emergency care nurses operating within the specified setting actively participated in this research. Data Collection Tools: Two tools were used for data collection. The first, an interview questionnaire, aimed to assess nurses' total knowledge toward the administration of nebulization therapy. The second, an observational checklist, to assess nurses' practical skills during nebulization therapy administration. Results: The study brought to light a substantial percentage (80.0%) of nurses exhibiting an unsatisfactory level of total knowledge concerning the administration of nebulization therapy. Additionally, 86.7% of the nurses showed inadequate practice in administering nebulization therapy. Conclusion: A discernible trend emerged, pointing to the prevalent inadequacy in knowledge and suboptimal practical application among the studied nurses in the administration of nebulization therapy. Furthermore, a significantly positive correlation was established between nurses' overall knowledge and their total practice in nebulization therapy, particularly concerning mechanical ventilation. Recommendations: The study strongly advocates for the development of customized training programs designed to enhance nurses' understanding of nebulizer devices. Moreover, the establishment of team of professionals able to do regular assessment of nurses' comprehension of inhaler devices, Sustained educational courses, with a focus on the correct inhaler techniques for respiratory nurses, are essential to optimize the utilization of these devices.