This study examined the predictive influence of spirituality and physical health on depression, anxiety, and stress among undergraduate students during their first full return to face-to-face learning after the COVID-19 pandemic. Anchored on the Biopsychosocial Model, SPIRE Model, and Health Hexagonal Model, a complex correlational design was employed using multiple linear regression analysis. Data were collected from 1,760 freshmen and sophomore students enrolled in 24 academic programs at a state university in the Philippines. Three validated instruments-the DASS-21, the Spirituality Scale, and the Physical Health Questionnaire-were administered. Findings revealed that spirituality, particularly the dimension of self-discovery, was a significant protective factor against depression, anxiety, and stress. In contrast, physical health concerns such as sleep disturbances, gastrointestinal problems, and respiratory infections were substantial risk factors across all three psychological outcomes. These results affirm the multifaceted nature of mental wellness and highlight the importance of integrating spiritual and physical dimensions in designing context-sensitive mental health interventions for higher education. The study contributes novel insights from the Philippine context to the growing global discourse on student mental health and underscores the value of holistic, culturally grounded approaches in supporting psychological well-being in post-pandemic academic transitions.