Acute myeloid leukaemia (AML) is a genetically diverse malignancy with a high incidence in Pakistan. But patients rarely benefit from personalized care due to the unavailability of molecular diagnostics. This study aims to identify actionable genetic variants in adult Pakistani AML patients by using the inDx^TM Extended AML/myelodysplastic syndrome panel for targeted next generation sequencing (NGS). Nine patients were included (median age = 42 years, 77.8% males). Mutations were found in six (66.7%) patients. The total number of mutations was 13 and these mutated 11 different genes, nine genes being affected in single cases (7.7%) and two genes: WT1 and DNMT3A, were mutated in two cases (15.4% each). Missense mutations constituted 69.2% of all 13 mutations. The variant allele frequencies for these mutations ranged from 7% to 54%. A number of clinically important mutations were observed, including an adverse WT1 variant, a favourable NPM1 mutation, targetable IDH1/JAK2 dual mutations and a myelodysplasia-related U2AF1 mutation. Co-mutation of DNMT3A with KRAS/NRAS or NPM1 indicated complex clonal dynamics. One of the three patients with no detectable mutations on NGS, was found Breakpoint cluster region-abelson murine leukaemia viral oncogene homolog 1-positive through polymerase chain reaction. This highlights the limitations of NGS panel, and advocates for the need for a multi-layered diagnostic approach. These findings support the viability of NGS in detecting clinically significant mutations in low-resource settings to guide risk stratification and personalized treatment planning. This study highlights the need for broader NGS integration in routine care and larger regional studies to improve AML management in Pakistan.