Recent advancements in genomic sciences and precision medicine have led to improved regulatory guidance for pharmacogenomics, particularly in the field of cancer therapies. Polymorphisms in genes that encode drug metabolizing enzymes and membrane transporters can cause marked interindividual variations in the absorption, distribution, metabolism, and excretion of anticancer drugs, with important implications for their therapeutic efficacy and potential adverse effects. Various ATP-binding cassette (ABC) and solute carrier (SLC) transporters have been identified as crucial components in this process, serving as gatekeepers across cellular barriers in different tissues. Single-nucleotide polymorphisms (SNPs) associated with these transporters can modify their expression or function, potentially leading to unpredictable clinical outcomes in terms of toxicity and efficacy of anticancer drugs. Transporters with broad substrate specificities have received the most attention in drug development, treatment optimization, and dose individualization. This chapter examines the impact of clinically relevant pharmacogenomics focusing on ABC and SLC transporters on the response of anticancer drugs in humans. It discusses their structure, function, and genetic variations to provide a better understanding of their role in cancer therapy.