Background: Ventilator-associated pneumonia (VAP) is a common nosocomial infection in intensive care units, associated with high morbidity and mortality. Stenotrophomonas maltophilia has emerged as an opportunistic pathogen in critically ill patients, particularly following prolonged mechanical ventilation and prior antibiotic exposure. Methods: We conducted a retrospective multicenter study over a 4-year period in three intensive care units in France. Adult patients with VAP caused by S. maltophilia were included. Clinical, microbiological, and therapeutic data were collected. The primary outcome was 28-day mortality. Results: Among 293 VAP episodes caused by non-fermenting Gram-negative bacilli, 28 (9.55%) were due to S. maltophilia. Patients were elderly, highly comorbid, and severely ill, with a high rate of septic shock (71.1%). Polymicrobial infections were frequent (75%), mainly involving Enterobacterales. Empirical antibiotic therapy was active in only 14.3% of cases. Targeted therapy mainly relied on trimethoprim–sulfamethoxazole or levofloxacin. The 28-day mortality rate was 60.7%, with early deaths observed after diagnosis. Conclusion: S. maltophilia VAP occurs in high-risk ICU patients and is associated with frequent polymicrobial infections, inadequate empirical therapy, and high mortality, highlighting the need for improved management strategies.