Background: Managing cancer-related pain poses significant challenges, prompting research into alternative approaches such as the study of ketamine. This systematic review aims to analyze and summarize the impact of ketamine as an adjuvant to opioid therapy for cancer-related pain. Methods: We conducted a literature review in MEDLINE, EMBASE, and Scopus, spanning from January 1, 1982, to October 20, 2022. Abstracts were screened against inclusion criteria, and eligible studies underwent a thorough full-text review. Data were extracted from the included studies, and a framework analysis approach was employed to summarize the evidence regarding ketamine's use in patients with cancer. The quality of included studies was assessed using the NIH Quality Assessment Tool for controlled intervention studies. Results: A total of 22 studies conducted between 2001 and 2019 were included, all assessed as having good quality. Three studies focusing on intrathecal administration of ketamine following oncological surgery demonstrated a substantial improvement in pain scores and a reduction in postoperative morphine requirements. Two studies exploring intramuscular use concluded that it led to improved pain scores. In contrast, three studies on subcutaneous administration and two studies on topical ketamine did not exhibit a significant impact on reducing pain scores or alleviating chemotherapy-induced peripheral neuropathy. Findings from two studies on oral administration and eight studies on intravenous administration indicated that intravenous ketamine reduced postoperative morphine requirements, while oral ketamine had no discernible effect on lowering pain scores. Conclusions: The use of intrathecal ketamine demonstrates significant improvement in post-op oncological pain and refractory cancer pain, resulting in lowered pain scores and decreased morphine requirements. Further research is essential to ascertain the extent to which incorporating ketamine with opioids in cancer pain treatment can enhance pain outcomes, especially in morphine-tolerant patients.