Background <p>Childhood cancer is a growing public health concern in low- and middle-income countries (LMICs), where over two-thirds of global pediatric cancer cases occur. Despite advances in diagnosis and treatment, malnutrition remains a major barrier to achieving better outcomes. This study aimed to assess the magnitude of undernutrition and identify barriers to optimal nutrition among pediatric patients with cancer receiving treatment at a major referral hospital in Tanzania.</p> Methods <p>Two study populations were recruited: pediatric patients with cancer and their primary caregivers. Children were assessed for undernutrition using anthropometric indicators, including mid-upper arm circumference, weight-for-age, height-for-age, body mass index-for-age Z-score, and triceps skinfold thickness. Nutritional biomarkers, including serum albumin, total protein, hemoglobin, and mean corpuscular volume, were also evaluated. Caregivers completed structured questionnaires adapted from the Hunger Vital Sign™ and the United Nations Food and Agriculture Organization Nutrition-related Knowledge, Attitude, and Practices Questionnaire to assess the risk of food insecurity and caregiver nutrition knowledge and perceptions. Binary logistic regression was used to explore predictors of undernutrition.</p> Results <p>A total of 65 pediatric patients were enrolled, of whom 41.54% were classified as undernourished based on at least one anthropometric indicator below age-specific thresholds. Although 44.62% had low serum albumin and 30.77% had low total protein, these biomarkers may reflect overall illness rather than nutritional deficiency alone. Anemia was observed in 53.85% of children under 5 and 38.46% of those aged 5 and older. Logistic regression showed that undernutrition was more likely among children aged 5–10 and &gt; 10&#xa0;years compared to those &lt; 5&#xa0;years (OR: 1.80; 95% CI: 0.88–3.68; <i>p</i> = 0.109), while anemia showed an inverse and unexpected association (OR: 0.15; 95% CI: 0.02–1.44; <i>p</i> = 0.100); however, neither was statistically significant. The risk of food insecurity was identified in 78.4% of households. Caregivers not at risk demonstrated significantly better nutrition knowledge and more positive perceptions than those at risk.</p> Conclusion <p>Undernutrition is common among pediatric patients with cancer and may be influenced by clinical and socioeconomic factors, including anemia, caregiver knowledge, and household food insecurity.</p> Trial Registration <p>This study is not a clinical trial and does not require registration. Clinical trial number: not applicable.</p>