Achieving military mission objectives requires high levels of performance from Airmen who operate under extreme physical and cognitive demands. Thus, there is a critical need to establish scientific interventions to enhance physical fitness and cognitive performance-promoting the resilience of Airmen and aiding in mission success. We therefore conducted a comprehensive, 12-week randomized controlled trial in active-duty Air Force Airmen (n = 148) to compare the efficacy of a multimodal intervention comprised of high-intensity interval aerobic fitness and strength training paired with a novel nutritional supplement [comprised of β-hydroxy β-methylbutyrate (HMB), lutein, phospholipids, DHA and selected micronutrients including B12 and folic acid] to high-intensity interval aerobic fitness and strength training paired with a standard of care placebo beverage. The exercise intervention alone improved several dimensions of physical fitness [strength and endurance (+ 8.3%), power (+ 0.85%), mobility and stability (+ 22%), heart rate (- 1.1%) and lean muscle mass (+ 1.4%)] and cognitive function [(episodic memory (+ 9.5%), processing efficiency (+ 7.5%), executive function reaction time (- 4.8%) and fluid intelligence accuracy (+ 19.5%)]. Relative to exercise training alone, the multimodal fitness and nutritional intervention further improved working memory (+ 9.0%), fluid intelligence reaction time (- 7.7%), processing efficiency (+ 1.8%), heart rate (- 2.4%) and lean muscle mass (+ 1.5%). These findings establish the efficacy of a multimodal intervention that incorporates aerobic fitness and strength training with a novel nutritional supplement to enhance military performance objectives and to provide optimal exercise training and nutritional support for the modern warfighter.