Abstract Introduction/Objective Pediatric Acute Myeloid Leukemia (AML) is a rare diagnosis that once carried a poor prognosis, but with recent improvement, the survival rate now reaches 80%. Although studies of most genetic mechanisms of AML involved adult studies, but dissimilar mutational profiles and treatment responses in pediatric patients have become evident. Information regarding pediatric AML-specific whole genome sequencing, a prognostic prediction system, and overall survival is limited. Hence, we aimed to analyze the genomic profile, epidemiological characteristics, and overall survival of pediatric AML. Methods/Case Report We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study genetic mutations associated with pediatric AML. Epidemiological characteristics and genetic profiles available on cBioportal were evaluated. Gene mutations with the most statistically significant shortest overall survival and survival in days from the samples were used for gene query, and survival rate with the most common mutations was calculated. Log-rank test and Kaplan–Meier estimators were used in analyzing the survival function. Patients with two or more overlapping mutations were excluded. Results (if a Case Study enter NA) We identified 899 patients with Pediatric AML, out of 886 had all demographic data available, 50.8% were males, 71.6% were Caucasian, and 11.3% were African American. 568 (63.2%) were alive, and 318 (35.4%) were deceased. 159 patients were diagnosed at less than or equal to 2 years of age, and 150 patients had 80-90% blasts in their samples. 440 (42.9%) had relapse of disease at the bone marrow, whereas 72 (7.0%) had relapse at other sites. The common mutations associated with reduced survival were C4ORF36, HERC5, GPRIN3, NFKB1, NUP88, QRFPR, SPRY1, and UNC5C. Median survival data of patients was available for GPRIN3, NFKB1, NUP88, SPRY1, UNC5C, and was 25.00, 11.00, 15.00, 59.00, and 14.00 months respectively. Comparison with the unaltered group was not available (p < 0.0001). Survival was lowest amongst NFKB1 (11.00 months), NUP88 (15.00 months), and UNC5C (14.00 months). In survival analysis, the same genes were associated with lowest survival after initial diagnosis (p = 7.301e-4). Conclusion Our study found that NFKB1, NUP88, and UNC5C genes were associated with the worst prognosis in pediatric AML with median survival of 11.00, 15.00, and 14.00 months. Furthermore it may result in improve the prognosis of these patients.