Currently, ketamine is used in treating multiple pain, mental health, and substance abuse disorders due to rapid-acting analgesic and antidepressant effects. Its limited short-term durability has motivated research into the potential synergistic actions between ketamine and psychotherapy to sustain benefits. This systematic review on ketamine-assisted psychotherapy (KAP) summarizes existing evidence regarding present-day practices. Through rigorous review, seventeen articles that included 603 participants were identified. From available KAP publications, it is apparent that combined treatments can, in specific circumstances, initiate and prolong clinically significant reductions in pain, anxiety, and depressive symptoms, while encouraging rapport and treatment engagement, and promoting abstinence in patients addicted to other substances. Despite much variance in how KAP is applied (route of ketamine administration, ketamine dosage/frequency, psychotherapy modality, overall treatment length), these findings suggest psychotherapy, provided before, during, and following ketamine sessions, can maximize and prolong benefits. Additional large-scale randomized control trials are warranted to understand better the mutually influential relationships between psychotherapy and ketamine in optimizing responsiveness and sustaining long-term benefits in patients with chronic pain. Such investigations will assist in developing standardized practices and maintenance programs.