Little is known about effective interventions to reduce aggressive end-of-life care in patients with cancer. We did a systematic review to assess what interventions are associated with reductions in aggressive end-of-life cancer care. We searched MEDLINE, CINAHL, Embase, Scopus, and PsychINFO for randomised control trials (RCTs), quasi-experimental, and observational studies published before Jan 19, 2018, which aimed to improve measures of aggressive end-of-life care for patients with cancer. We developed a taxonomy of interventions using the Systems Engineering Initiative for Patient Safety (SEIPS) model to summarise existing interventions that addressed aggressive care for patients with cancer. Of the 6451 studies identified by our search, five RCTs and 31 observational studies met the final inclusion criteria. Using the SEIPS framework, 16 subcategories of interventions were identified. With the exception of documentation of end-of-life discussions in the electronic medical record, no single intervention type or SEIPS domain led to consistent improvements in aggressive end-of-life care measures. The ability to discern the interventions’ effectiveness was limited by inconsistent use of validated measures of aggressive care. Seven (23%) of 31 observational studies and no RCTs were at low risk of bias according to Cochrane’s Risk of Bias tool. Evidence for improving aggressive end-of-life cancer care is limited by the absence of standardised measurements and poor study design. Policies and studies to address the gaps present in end-of-life care for cancer are necessary.