Concern for the psycho-physical well-being of university students is increasingly the focus of attention in universities, not least because of the last two years of the pandemic, which exacerbated a previous situation of malaise. Therefore, the present study set out to investigate the relationship between certain contextual and personal demands and resources, and students’ engagement and emotional exhaustion. The study involved 10,212 students from 11 Italian universities, 59% of whom were attending a three-year course; participants completed an online questionnaire during the second lockdown. The results showed that workload and internet addiction are positively associated with exhaustion and negatively with engagement; in contrast, academic fit is negatively associated with exhaustion and positively with engagement. The data seem to suggest that the profile of the most engaged student who is least at risk of emotional exhaustion has: an older age, lower levels of workload and internet addiction, and higher academic fit. The results confirm the importance of effective measures and policies: implementing treatment and prevention services, support spaces, counselling centres, investing in guidance interventions, and training for both students and teachers.