Background: Social determinants of health (SDOH) interventions within clinical settings have been proposed to address health-related social needs, but few studies have explored intervention needs and challenges for Latinx families. This sequential mixed-methods study examined the effect of Developmental Understanding and Legal Collaboration for Everyone (DULCE), a 6-month SDOH intervention conducted in pediatric clinics in California and Florida. Methods: Using survey data collected among Latinx caregivers who participated in the DULCE evaluation (n = 393), we examined changes in caregivers’ depression, stress, and resilience, including differences by nativity. Qualitative interviews were conducted with DULCE participants (n = 16) across nativity to elucidate the components of the intervention that impacted caregiver outcomes. Results: DULCE led to significant increases in resilience among Latinx caregivers, especially immigrants, but no changes in depression or stress. Qualitative interviews illuminated that the following themes contributed to caregivers’ resilience through the DULCE program: trusted relationship with family specialist caseworkers, connection to critical resources, addressing postpartum depression and social isolation, building caregivers’ capacity to withstand challenges, and bolstering caregivers’ confidence to seek resources independently. Discussion: Pediatric SDOH interventions are a promising strategy to support Latinx families in early childhood. Effective interventions for Latinx families, however, require strategies that pair resource connection with relationship building, address immigrants’ and Latinx system avoidance, and incorporate additional supports or boosters for families experiencing extreme stress.