Background <p>Patients with Epidermolysis Bullosa (EB) face extensive and complex challenges, and nurses play a decisive role in providing care for them and educating their families. However, the multifaceted nature of EB care introduces significant challenges for nurses.</p> Objective <p>This study aimed to explore the challenges nurses face in caring for patients with EB.</p> Methods <p>This is a qualitative study conducted from August to December 2024. Semi-structured, in-depth, face-to-face interviews were conducted with 15 nurses who provided care to patients with EB in Urmia, Northwest Iran. Data were analyzed using the conventional content analysis approach proposed by Graneheim and Lundman (2004).</p> Results <p>Data analysis revealed three main categories of challenges faced by nurses in caring for patients with EB: “<i>Problematic Parental Reactions</i>” which includes harmful parental demands, difficult initial encounters, and parental detachment; “<i>Care Avoidance</i>” encompassing arduous routine care and the psycho-erosive nature of care; and “<i>The Forgotten Illness</i>” characterized by limited organizational support and insufficient organizational knowledge enhancement.</p> Conclusion <p>Caring for EB patients presents numerous challenges for nurses, including Problematic Parental Reactions, care avoidance, and the broader context of a forgotten illness. Parental demands, difficult initial encounters, and parental detachment complicate the care, while the demanding and psycho-erosive nature of daily tasks exacerbates nurse fatigue. Furthermore, organizational neglect—stemming from inadequate resources and insufficient training—intensifies these difficulties. These findings highlight the need for targeted training programs and systemic support to address the unique difficulties inherent in caring for patients with EB.</p>