(1) Background: This mixed-method study aims to identify and describe factors associated with acute and long-term parenting stressors and coping strategies in caregivers of children with intraluminal pulmonary vein stenosis (PVS). (2) Methods: Parents of children with severe PVS were recruited from a large quaternary hospital to complete a survey that included demographics, the Pediatric Inventory for Parents (PIP), and the Coping Health Inventory for Parents (CHIP). We determined the Social Vulnerability Index (SVI) based on self-reported home address. A subset of caregivers completed a 60 min semi-structured interview via Zoom exploring the impact their child's diagnosis had on their family; experience managing stress in the hospital and at home; current resources and processes for coping; and potential recommendations for hospitals to build resilience and coping. We used multivariable linear regression to examine the association between SVI and parental stress and coping while adjusting for possible confounders. Thematic analysis identified themes related to stress and coping. Finally, we assessed instances of convergence and difference between the qualitative and quantitative results. (3) Results: Participants included 32 caregivers who were 91% female with a mean age of 39 years. The children of participants were 66% female, with a mean age of five years. The parents reported a high amount of stress with an average PIP score of 120, nearly 46 points higher than similar studies in the congenital heart community. We observed no significant associations between SVI and either parental stress or coping in adjusted models. We identified 13 themes, including medical care, hospital, family, support systems, and home medical routine or support. (4) Conclusions: Our study found high levels of illness-related parental stress among caregivers of children with PVS. Stress evolved over time from what caregivers described as 'survival mode' to a future-oriented outlook. Currently, caregivers rely heavily on support networks that are not available to all caregivers or may experience strain over time. Caregivers indicated that communication and parental role functioning were coping strategies that could be better supported by providers and health systems.