Mechanical insufflation-exsufflation (MI-E) has long been used by the neuromuscular population. It is becoming more common to employ MI-E in critically ill patients who are receiving invasive ventilation. Their objective was to map the most recent studies on the use of MI-E in critically ill patients who are invasively ventilated. Two authors independently searched the following electronic databases between January 1990 and April 2021: PROSPERO, Cochrane Library, ISI Web of Science, MEDLINE, Embase, and CINAHL via the Ovid platform. The inclusion criteria were adult critically ill patients requiring invasive ventilation, the use of MI-E, a study design utilizing original data, and publications from 1990 or later. A customized extraction form was utilized by two writers to collect the information independently. They used the Mixed Methods approach to determine the bias risk. The theoretical domains framework is used in the interpretation of qualitative data. A total of 3,090 citations were retrieved, and 28 of them were used to extract data. The main justifications for employing MI-E during invasive breathing were the presence of secretions and mucus blockage (13/28, 46%). Some contraindications to using high positive pressure were believed to exist (18/28, 68%). The protocolized MI-E settings that were most frequently utilized had a pressure of about 40 cm H2O, and information about the prescription’s time, flow, and frequency was rarely made public. The outcomes included re-intubation rate, the weight of moist sputum, and pulmonary mechanics. Three studies were the only ones to record adverse effects. Qualitative findings indicate that the main barrier to the adoption of MI-E in this subject group was a lack of knowledge and skill. They concluded that there is little consistency in the application and reporting of MI-E, precluding recommendations for best practices.