Purpose: Time toxicity—the time patients spend receiving treatment, managing side effects, attending follow-ups and undergoing rehabilitation—is increasingly recognised as an important burden of cancer care. While time toxicity has been studied in routine clinical settings, it has rarely been quantified among patients with cancer enrolled in pharmacotherapy clinical trials. This systematic review aims to quantify time toxicity in this population. Design: We searched Ovid MEDLINE, Embase and Cochrane CENTRAL from inception to 12 June 2025. Studies were included if they reported time toxicity among patients with cancer enrolled in clinical trials. Time toxicity was defined as calendar days with healthcare contact. Primary outcomes were (1) total days, (2) planned days and (3) unplanned days per month. Study quality was assessed using the Joanna Briggs Institute’s (JBI) Checklist for Cohort Studies. Results: Four retrospective studies reporting on an aggregate of 1809 patients were included. Two studies had low risk for bias and two had unclear risk of bias. Patients experienced time toxicity a mean of 7.6 days per month, with the highest burden in the first month of trial participation. Planned and unplanned days averaged 2.2 and 2.0 days per month, respectively. The ratio of planned to unplanned days remained consistent over time. Conclusions: Time toxicity is a substantial, under-recognised burden in cancer pharmacotherapy trials—approximately two times that experienced by non-participants. Its measurement and mitigation should be prioritised to improve patient-centred care, support shared decision-making and inform trial design, policy and consent processes. Registration: Study protocol preregistration: https://doi.org/10.17605/OSF.IO/BVY7C.