PURPOSE: Approximately 30% of patients with cancer who have pain have symptomatic improvement within 1 month using conventional pain management strategies. Engaging clinical pharmacists in palliative medicine (PM) and use of pharmacogenomic testing may improve cancer pain management. METHODS: Adult patients with cancer with uncontrolled pain had baseline assessments performed by PM providers using the Edmonton Symptom Assessment Scale. Pharmacotherapy was initiated or modified accordingly. A subset of patients consented to pharmacogenomic testing. The first pharmacy assessment occurred within 1 week of baseline and a second assessment was done within another week if intervention was required. Each patient’s final visit was at 1 month. Pain improvement rate (a reduction of two or more points on a 0-to-10 pain scale) from baseline to final visit was compared applying the Fisher exact test to published historical control data, and between patients with and without pharmacogenomic testing. Multivariate logistic regression identified pain improvement covariates. RESULTS: Of 142 patients undergoing pharmacy assessments, 53% had pain improvement compared with 30% in historical control subjects ( P < .001). Pain improvement was not different between those who received (n = 43) and did not receive (n = 99) pharmacogenomics testing (56% v 52%; P = .716). However, of 15 patients with an actionable genotype, 73% had pain improvement. Higher baseline pain (odds ratio [OR], 1.79; 95% CI, 1.43 to 2.24; P < .001), black or other race (OR, 0.42; 95% CI, 0.18 to 0.95; P = .04), and performance status 3 or 4 (OR, 0.18; 95% CI, 0.04 to 0.83; P = .03) were associated with odds of pain improvement, but pharmacogenomic testing was not ( P = .64). CONCLUSION: Including pharmacists in PM improves pain management effectiveness. Although pharmacogenomics did not statistically improve pain, a subset of patients with actionable genotypes may have benefited, warranting larger and randomized studies.