Background: Oral chemotherapy (OC) has gained increasing popularity due to perceived advantages in convenience and toxicity profiles compared to conventional chemotherapy. Based on ASCO/ONS guidelines, we established standard operating procedures (SOPs) and a nurse-led oral chemotherapy clinic to guide the safe administration and monitoring of OC in our outpatient hematology/oncology clinic. Methods: A dedicated oral chemotherapy clinic led by a certified chemotherapy nurse was created to ensure standard metrics identified in the ASCO/ONS guidelines were met with each patient visit. Fifty-seven charts were randomly selected for a 3-month post intervention analysis. Results: The OC nurse identified toxicities in 17/57 (30%) of cases prompting notification of the ordering physician. This led to modifications in supportive medications in 9/17 (53%) of cases. Dose modifications occurred in 6/17 (35%). Informed consent documentation was available in only 36/57 (63%) charts. Necessary lab work was missing in 7/57 (12%) cases, prompting completion prior to OC release. An incorrect OC was dispensed by pharmacy in one case. Each visit took approximately 30 minutes from check-in to release of OC. All patients received OC education specific to their regimen. Conclusions: A dedicated visit with an OC nurse provided a vital means to ensure patient education, safe prescribing, proper dispensing, and monitoring of toxicities. Nursing identified the need for supportive care interventions and dose reductions in over 25% of charts which mitigated potential adverse events. Due to average time required for each patient encounter, we found this process to be unsustainable with increasing needs and limited resources. Thus, we revised our SOP to include a checklist of standard ASCO/ONS metrics. We also decreased the follow-up requirement for patients who did not require further intense monitoring after 6 months. Ongoing efforts will be made to ensure the effectiveness of this program. Future interventions will also capture cost effectiveness to establish a fair compensation model for reimbursement and justification of clinical support required to enforce current administration safety standards.