Caregiving is a complex occupation, with a significant impact for informal caregivers (IC). Stress-process models propose a framework that considers that this impact depends on primary and secondary stressors, but also on the IC situation appraisal. This work aimed to verify: whether being, or not, an IC of an individual with dementia influenced the relationship between family functioning and burnout; the association between neuropsychiatric symptoms of the individual with dementia and IC burnout and whether the IC burden and perceived family functioning had a mediating role in such relationship. This cross-sectional study investigated differences in family functioning and its association with burnout between IC and non-IC. For IC specifically, the study examined a mediation model to explore the possibility of neuropsychiatric symptoms indirectly affecting IC burnout through the impact on family functioning and burden. Measures included the Copenhagen Burnout Inventory, the McMaster Family Assessment Device, the Neuropsychiatric Inventory, and the Zarit Burden Interview. Results showed an association between poorer family function and high burnout, specifically in IC. They also showed that burden mediated the relationship between neuropsychiatric symptoms and burnout. The findings offer a significant contribution to the growing knowledge about the relationship between stressors associated with informal caregiving in dementia context, such as neuropsychiatric symptoms and its outcomes, like burnout.