Background: This study aimed to determine whether pre-operative medication use is associated with unplanned 30-day readmission in elderly people undergoing cancer surgery. Methods: Patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment were included. Comparisons of variables between patients with readmission and those without readmission were performed by univariate and multivariate analyses. Results: A total of 473 patients were included. Multivariate analysis showed that pre-operative discontinuation-requiring medications (PDRMs) and gastrointestinal/hepato-pancreato-biliary (GI/HPB) cancer were significant factors for 30-day readmission. PDRM increased the risk of readmission by about 2.2-fold. Attributable risk of PDRM to readmission was around 55%. The adjusted odds ratio and attributable risk for GI/HPB surgery was 3.4 (95% CI 1.0–11.5) and 70.8%, respectively. Conclusions: Medication use has an impact on unplanned 30-day readmission in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.