Background <p>Cancer is a life-threatening challenge for children with leukemia, and hope is essential for coping with it.</p> Objective <p>The aim of this study was to explore the experiences of Iranian children with leukemia that diminish their sense of hope.</p> Interventions/methods <p>This qualitative study used a content analysis approach. Data were collected through art-based interviews with 23 school-aged children with leukemia at Tehran Children’s Medical Center Hospital. The data were analyzed in three stages: identifying semantic units, classifying and labeling codes, and reporting results.</p> Results <p>The analysis yielded three main themes: physical problems (8 codes), limitations related to treatment protocols and the hospital environment (21 codes), and peers’ negative reactions (3 codes). These factors were found to reduce hope among children living with leukemia.</p> Conclusions <p>Hospitalization and treatment protocols are often perceived a hopeless experience for children with leukemia. Hope-based interventions should be considered to enhance their quality of life.</p> Implications for practice <p>In providing holistic care to children with leukemia, healthcare providers, particularly nurses, should inspire hope by recognizing and addressing children’s unique experiences.</p>