University students commonly experience reduced cardiorespiratory fitness and elevated psychological stress due to sedentary lifestyles and academic pressure. Although high-intensity interval training (HIIT) and B-vitamin supplementation are individually known to enhance physiological and psychological health, their combined effects remain underexplored. This systematically guided narrative review synthesizes current evidence on how HIIT and B-vitamin supplementation may interact to influence aerobic capacity, metabolic regulation, and stress resilience. Existing studies demonstrate that HIIT improves VO₂max, mitochondrial efficiency, and HPA-axis stability, while B-vitamins facilitate energy metabolism, neurotransmitter synthesis, and oxidative stress control. Together, these mechanisms suggest a potential synergistic interaction that enhances endurance and psychological well-being through coordinated metabolic and neuroendocrine pathways. However, this synergy remains a theoretical model requiring empirical validation through controlled trials. The findings highlight the importance of integrated exercise–nutrition strategies in promoting health and resilience among college populations.