A dangerous infection contracted in hospitals, ventilator-associated pneumonia is frequently caused by bacteria that are resistant to several drugs. It is one of the main reasons why patients in intensive care units become ill or die. This research aimed to determine the most effective empirical therapy of antibiotics for better ventilator-associated pneumonia control and to improve patient outcomes by using the minimal inhibitory concentration method and the Ameri–Ziaei double antibiotic synergism test and by observing the clinical responses to both single and combination therapies. Patients between the ages of one month and twelve who had been diagnosed with ventilator-associated pneumonia and had been on mechanical ventilation for more than 48 h were included in the study, which was carried out in the Pediatric Intensive Care Unit at Cairo University’s Hospital. When ventilator-associated pneumonia is suspected, it is critical to start appropriate antibiotic therapy as soon as possible. This is especially important in cases where multidrug-resistant Gram-negative infections may develop. Although using Polymyxins alone or in combination is effective, it is important to closely monitor their administration to prevent resistance from increasing. The combination therapy that showed the greatest improvement was a mix of aminoglycosides, quinolones, and β-lactams. A combination of aminoglycosides and dual β-lactams came next. Although the optimal duration of antibiotic treatment for ventilator-associated pneumonia is still unknown, treatments longer than seven days are usually required to eradicate MDR P. aeruginosa or A. baumannii completely.