Cardio-oncology is an emerging multidisciplinary field intended to mitigate and manage cardiovascular side effects and risks associated with cancer therapies. Clinician awareness of drug interaction management among cancer treatments, cardiovascular medications, and supportive care agents is important for optimizing efficacy and safety. Historically, chemotherapies have been associated with pharmacodynamic interactions with few, but important, pharmacokinetic interactions. The advent of oral targeted inhibitors has introduced more complex pharmacokinetic interactions, especially via cytochrome P450 pathways. Given the accelerated development of oncology therapies, clinicians need to be familiar with reviewing multiple sources for interaction information as well as adjusting and monitoring regimens when contending with drug interaction challenges.