Background: Pharmacogenomics (PGx) testing is used increasingly in cancer supportive care for drug and dose selection, and side effects prediction with antidepressants, antiemetics, and pain medications. Genetic variants in genes that encode for drug metabolizing enzymes (CYPs), transporters (SLC6A4) and drug receptors (HTR2A, OPRM1, etc) are well known for these medications. They contribute to inter-individual differences in medication safety and efficacy. We report on their frequency and effect on supportive care drugs in patients with solid tumors. Methods: Between 06/06/19 and 12/18/19, solid tumor cancer patients at Mayo Clinic Arizona were enrolled in a PGx prospective study. They were genotyped using a multi-gene panel, OneOme RightMed. The panel assessed 27 genes, including CYP2C9, CYP2C19, CYP2D6, CYP3A4, COMT, OPRM1, GRIK4, HTR2A, SLC6A4, associated with pain medications, antidepressants, and antiemetics. PGx pharmacist provided medication recommendations and dose adjustments based on PGx test results and concurrent medications. Results: 200 patients were swabbed and 196 patients were genotyped. The results were available within 5 days. All patients were also assessed for pheno-conversion (drug-drug-gene interactions) by a pharmacist. Recommendations were made based on predicted phenotype. Various solid tumor types were represented, including prostate (19.9%), colorectal (17.9%), melanoma (14.8%), and others (47.4%). Median age was 65 with 59.2% patients being male and 40.85% female. All had at least one actionable polymorphism related to these medications. The most significant findings were related to CYP2C19 and CYP2D6 genes. Of 196 patients, a total of 132 (67.3%) had other than normal CYP2D6 metabolizer phenotype and 112 (57.1%) had other than normal CYP2C19 metabolizer phenotype. Based on these genotypes, alternatives to pain medications were recommended for 37 patients, to ondansetron in 9 patients, and to anti-depressants in 51 patients. Conclusions: Genetic variants were commonly found that affect supportive care medications used in oncology practice and contribute to inter-individual differences associated with increased risk of adverse drug effects and reduced efficacy. PGx guided recommendation may help physicians in individualizing medication treatment outcomes for patients with different cancer types and with polypharmacy. PGx trained pharmacist can serve as a valuable asset in optimizing personalized medication management.