Nutritional status (NS) in children with cancer may impact a wide range of outcomes, and remediation of under and over-nutrition may potentially improve outcomes. Children with cancer at our centre were classified as undernourished (UN) body mass index (BMI Z-score ≤−2 standard deviations (SD) World Health Organisation (WHO) or mid-upper-arm circumference (MUAC) <12.5 cm for <5 years (WHO) or <25th percentile for >5 years (Frisancho)), well-nourished (WN) (BMI Z-score −1 SD to +1 SD or MUAC 12.5–13.5 cm for <5 years or 25–50th percentile for >5 years) and over-nourished (ON) (BMI Z-score ≥+1 SD or MUAC ≥75th percentile for >5 years). NS was assessed at three time-points: diagnosis, 3- and 6-month follow-up. Trends in NS and impact on outcomes (event-free survival (EFS) and overall survival) were analysed. At diagnosis (n = 2,086) and 6-month follow-up (n = 1,245), 30.9% and 41.7% were WN, 65.3% and 52.2% UN and 3.8% and 6.1% ON. During the course of treatment, 45.5% gained weight and 11.6% lost weight. The highest prevalence of undernutrition at diagnosis was seen in acute myeloid leukaemia (73.3%), lymphoma (68.8%) and bone tumours (68.7%). Two-year EFS was 71.3% ± 1.82% in WN children, 71.3% ± 5.19% in ON children and 68.4% ± 1.28% in children UN at diagnosis (p = 0.004). Children who gained weight between diagnosis and follow-up had a 2-year EFS of 82.8% ± 1.60% versus 76% ± 1.70% in those without weight gain (p = 0.022). Undernutrition at diagnosis as well as during treatment leads to increased relapse as well as mortality. Weight gain and improved NS appear to impact clinical outcomes, highlighting the need for targeted nutritional interventions in children with cancer.