Abstract Exome sequencing (ES) has emerged as an essential tool in the evaluation of neurodevelopmental disorders (NDD) of unknown etiology. Genome sequencing (GS) offers advantages over ES due to improved detection of structural, copy number, repeat number and non‐coding variants. However, GS is less commonly utilized due to higher cost and more intense analysis. Here, we present nine cases of pediatric NDD that were molecularly diagnosed with GS between 2017 and 2022, following non‐diagnostic ES. All individuals presented with global developmental delay or regression. Other features present in our cohort included epilepsy, white matter abnormalities, brain malformation and dysmorphic features. Two cases were diagnosed on GS due to newly described gene‐disease relationship or variant reclassification ( MAPK8IP3, CHD3 ). Additional features missed on ES that were later detected on GS were: intermediate‐size deletions in three cases who underwent ES that were not validated for CNV detection, pathogenic variants within the non‐protein coding genes SNORD118 and RNU7‐1 , pathogenic variant within the promoter region of GJB1 , and a coding pathogenic variant within BCAP31 which was not sufficiently covered on ES. GS following non‐diagnostic ES led to the identification of pathogenic variants in this cohort of nine cases, four of which would not have been identified by reanalysis alone.