Childhood leukemia remains a significant public health concern as the leading cause of cancer-related morbidity and mortality in children. The continued rise in incidence can be attributed to a variety of environmental exposures as well as the complex heterogenous genetic profile. Understanding the disease pathophysiology and drug clinical pharmacology is effective in optimising long-term survival and reducing the risk of adverse drug reactions. The current challenges in drug resistance and toxicity can be addressed with personalised medicine. That is, tailoring drug administration to the individual to reduce the clinical effects of pharmacokinetic variability. Further research in pharmacogenomics and pharmacotranscriptomics will aid in developing effective therapies for the heterogenous genetic profile of Leukemia.