Despite harboring a high burden of cancer patients who are at high risk of potential drug-drug interactions (pDDIs), there is scarcity of published information about pDDIs in cancer patients from Pakistan. To evaluate frequency, pattern, mechanism and factors associated with pDDIs in cancer patients treated at a tertiary care hospital in Pakistan. In this cross-sectional analytical study, a total of 253 eligible ambulatory cancer patients treated at Center for Nuclear Medicine and Radiotherapy Hospital Quetta were evaluated for pDDIs using IBM Micromedex® Drug Interactions. SPSS (version 26) was used for conducting multivariate analysis to find factors associated with the presence pDDIs. A p-value <0.05 was considered statistically significant. A total of 141/253 (55.7%) patients were exposed to at-least one pDDI. A total of 251 pDDIs were noted with a median of one pDDI/per patient (interquartile range:1-2) Majority interactions were of major severity (72.9%), pharmacodynamic (49.8%) and had fair documentation level (64.1%). Anti-cancer drugs were involved in 73.0% pDDIs with doxorubicin as the most commonly involved (40.0%) anti-cancer followed by cyclophosphamide (27.6%) and cisplatin (13.5%). Potential cardiac adverse events made the bulk (33.8%) of predicted events. Receiving >2 anti-cancer (OR = 5.19, p-value = 0.001) and >6 ancillary drugs (OR = 4.16, p-value = 0.033) emerged as the risk factors of pDDIs. The prevalence of pDDIs was within the range reported in published literature. Solid medication review, availability of DDI detecting tools and clinical pharmacist, and paying special attention to the high-risk patients may reduce the frequency of pDDIs at the study site.