Emergency medicine clinicians face disproportionately high levels of burnout and mental health strain compared to other specialties. This study examined whether perceived resilience predicted reduced mental health strain following the COVID-19 Omicron surge and whether meaningful work mediated this relationship. Participants were 197 emergency medicine professionals at a large hospital system who completed monthly surveys during the pandemic. Perceived resilience and meaningful work were measured pre-Omicron surge, and mental health strain was measured post-surge. Results showed that higher perceived resilience significantly predicted lower mental health strain and that meaningful work explained 40% of this relationship. The findings emphasize that resilience matters and that its benefits are at least partly a function of meaningful work. Broader implications extend to organizations seeking to strengthen workforce well-being. Interventions should integrate resilience-building with practices that enhance purpose and meaning at work.