Cancer management, including supportive care, is complex and requires availability and synthesis of published and patient-specific data to make appropriate therapeutic decisions. Clinical decision support (CDS) may be an effective implementation strategy to support complex decision making although it is unclear whether it improves process outcomes, patient outcomes or both in cancer settings. We therefore conducted a systematic review to identify CDS that have been used to support therapeutic decision making in clinical cancer settings. Outcomes of interest included the effect of CDS on the process, such as clinician's decision making and effect on patient outcomes. Ten studies met inclusion criteria, with variability in the study design, setting, and intervention. Of the nine studies that measured process outcomes, five demonstrated significant improvement; and of the six that measured patient outcomes, four demonstrated significant improvement. All included studies utilized CDS that were informed by clinical practice guidelines. In conclusion, CDS to guide cancer therapeutic decision making is an understudied but promising area. Further research is needed.