Polypharmacy (PP) and hyperpolypharmacy (HPP), are prevalent among cancer patients and are associated with an increased risk of drug-drug interactions (DDI) and potentially inappropriate medications (PIM). This study aimed to characterize PP, HPP, DDI, and PIM in patients with hematological malignancies hospitalized for hematopoietic stem cell transplantation (HSCT) by introducing a novel metric: cumulative drug exposure. Clinical data warehouse (CDW) records were employed to develop algorithms that quantified patients’ cumulative exposure to these prescribing determinants during hospitalization. This entailed determining the number of days during the hospital stay when the patient was exposed to PP, HPP, PIM and/or DDI. For PIM and DDI, the number of PIMs or DDIs administered per day was taken into account in this calculation. Among 339 HSCT patients, PP and HPP were highly prevalent (over 67% of HSCT patients), almost all patients experienced DDI (over 98% of HSCT patients) and almost all elderly patients were exposed to PIM (over 98% of HSCT patients). Cumulative drug exposure differed between allogeneic and autologous HSCT patients, with allogeneic patients being more exposed to HPP (28.5 days vs 4.7 days for autologous HSCT patients) and DDI (255.6 days vs 58.4 for autologous HSCT patients). This study proposes a novel approach to assessing the impact of prescribing determinants on patient outcomes and provides insights for future research into the association between drug exposure and adverse events. Indeed, the use of cumulative drug exposure as a metric provides a comprehensive view of patient exposure throughout hospitalization, thereby enhancing understanding of the impact of prescribing practices on clinical outcomes.