Introduction Several studies reported that drug therapy problems (DTPs) were prevalent in cancer patients. These DTPs are still interfering with the desired treatment outcomes in patients with cancer. This study aimed to determine the prevalence, types and predictors of DTPs among paediatric acute lymphoblastic leukaemia (ALL) patients at Kenyatta National Hospital. Methods A retrospective cohort study was used to assess DTPs among ALL patients. Records of all eligible paediatric patients with ALL who received treatment in the facility between 1 January 2017 and 31 December 2021 were examined. A data abstraction tool was employed for data collection. The data entry and analysis were carried out by a statistical package for social sciences version 29.0 software. Frequency tables were utilised to present the key findings of the study. Binary logistic regression analysis was utilised to determine the predictors of DTPs. Results A total of 82 DTPs were identified with the most common type of DTP being adverse drug reaction (ADR; 59, 72.0%) and drug interaction (9, 11.0%). The most common ADRs identified were febrile neutropenia (20, 33.9%), nausea/vomiting (14, 23.7%) and anaemia (11, 18.6%). Patients with central nervous system disease (adjusted odds ratio [AOR] = 10.2, 95% CI = 1.2–85.8, p = 0.03) and treated with a combination of chemotherapy and radiotherapy (AOR = 13.5, 95% CI = 1.9–89.4, p = 0.01) were more likely to develop DTPs. Conclusion The study found that the prevalence of DTPs among paediatric ALL patients was high, with the most common DTPs being ADRs occurring in 72.0% of patients. Central nervous system metastasis and a combination of chemotherapy and radiation treatment regimens were statistically significant predictors of DTPs.