This chapter discusses the complex challenges faced by children with chronic illnesses, many of whom have developmental disabilities, during and after hospitalization. Drawing on Bronfenbrenner’s Ecological Systems Theory, it underscores the value of a holistic system-of-care approach. Hospitalization can disrupt daily routines, leading to social isolation, anxiety, and academic difficulties. Effective interventions include peer support and mentorship programs that foster resilience, belonging, and emotional well-being, along with family-to-family connections that offer guidance and validation. Psychoeducation and cognitive-behavioral therapies help families cope and improve functioning. School achievement is supported through hospital school programs, technology-assisted learning, and reintegration strategies that accommodate medical needs and build peer understanding. Collaboration among families, healthcare providers, and schools is crucial for medical regimen adherence, guided by tailored plans and ongoing communication. The chapter highlights gaps in research and calls for more studies on interventions that best promote resilience and quality of life for affected children.