Background: Musculoskeletal pain is a common and debilitating condition for cancer patients. Existing therapies for these pain conditions have substantial limitations. To identify an integrative approach to pain management, we conducted a systematic review to evaluate the safety and efficacy of a Tibetan herbal-based topical agent, CheeZheng Pain Relieving Plaster (PRP), for the treatment of osteoarthritis (OA) pain. Methods: We extracted citations from PubMed and Chinese databases (CNKI, WanFang Data, and CQVIP). We included randomized clinical trials evaluating the effectiveness and safety of CheeZheng PRP compared to conventional OA pain treatments. Results: Twenty-two randomized clinical trials (n = 2556 participants) compared CheeZheng PRP against nonsteroidal anti-inflammatory drugs (11), glucosamine (2), intraarticular corticosteroid (2), hyaluronic acid injections (6), and acetaminophen (1). Ten studies found a statistically greater effectiveness (assessed by ≥30% reduction in symptom severity) of CheeZheng PRP in improving OA pain (measured by the Visual Analogue Scale), stiffness, and function compared to control. Ten studies reported that 4.8% of participants experienced application site skin irritation that resolved after discontinuing the plaster. Randomization was not sufficiently described in most studies, and no placebo-controlled trials were identified. Conclusions: There is promising evidence for the safety and clinical effectiveness of CheeZheng PRP to treat OA; however, lack of placebo control and unclear descriptions of randomization increase the potential risk for bias. Future randomized, placebo-controlled trials are needed to establish the safety and efficacy of CheeZheng PRP for pain management in oncology settings.