The term “drug-drug interaction” (DDI) generally describes the occurrence when the therapeutic or harmful effects of a medication are changed by the simultaneous or prior administration of other pharmacologically active substances. These interactions can be generally categorized into two primary types: pharmacokinetic interactions (PKIs) and pharmacodynamic interactions (PDIs). Internationally, lung cancer remains among the most widespread and lethal malignancies, predominantly presenting as non-small cell lung cancer (NSCLC). Over the years, various anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (ALK-TKIs) have been formulated and swiftly integrated into the field of oncology for treating NSCLC. Crucially, intestinal CYP-450 enzymes play a pivotal role in metabolizing a diverse array of orally administered drugs, including ALK-TKIs. Hence, it is imperative to avoid their concurrent use with potent CYP3A inhibitors or inducers. Pharmacokinetic drug-drug interactions can occur at various phases of the drug-body interaction, including absorption, distribution, metabolism, and excretion. Multiple factors, including food, acid-reducing agents (ARAs), transporter inhibitors/inducers, and cytochrome P450 (CYP) inhibitors/inducers, may contribute to the induction of DDIs upon the ingestion of ALK-TKIs. Conversely, recent clinical evidence highlights the significance of addressing pharmacodynamic interactions when administering the ALK-TKI ceritinib. This chapter focuses on some potential DDIs associated with ALK-TKIs in clinical settings, underscoring the need to evaluate these interactions in patients undergoing ALK-TKI treatment. In essence, a systematic understanding of pharmacological interactions, especially concerning drug absorption, elimination, transport, and metabolism, can contribute to averting adverse effects of medications.