Public health emergencies such as the COVID-19 pandemic can further strain the mental health of informal caregivers who provide unpaid assistance to family members or friends who need support due to illness, disability, or aging. However, there is a lack of research exploring the resources and adaptive strategies that promote resilience in informal caregivers. This cross-sectional study used psychometric network analysis to model the interplay between coping strategies, emotion regulation, trait resilience, and anxiety and depression symptoms in 351 Italian informal caregivers. The results showed that coping through a positive attitude, emotional reappraisal, and trait resilience were the most central and interconnected nodes in the network. These adaptive strategies buffered against the negative impact of anxiety and depression symptoms, providing valuable insights into the mechanisms underlying resilience and well-being in informal caregivers. Clinically, it is crucial to assess and foster these resilience-promoting factors (positive attitude coping, cognitive reappraisal, and trait resilience) to help mitigate the mental health challenges faced by informal caregivers, especially in the context of public health crises such as the COVID-19 pandemic.