In oncology, and especially in the treatment of non-small-cell lung cancer (NSCLC), dose optimization is often a neglected part of precision medicine. Many drugs are still being administered in "one dose fits all" regimens or based on parameters that are often only minor determinants for systemic exposure. These dosing approaches often introduce additional pharmacokinetic variability and do not add to treatment outcomes. Fortunately, pharmacological knowledge is increasing, providing valuable information regarding the potential of, for example, therapeutic drug monitoring. This article focuses on the evidence for the most promising and easily implemented optimized dosing approaches for the small-molecule inhibitors, chemotherapeutic agents, and monoclonal antibodies as treatment options currently approved for NSCLC. Despite limitations such as investigations having been conducted in oncological diseases other than NSCLC or the retrospective origin of many analyses, an alternative dosing regimen could be beneficial for treatment outcomes, prescriber convenience, or financial burden on healthcare systems. This review of the literature provides recommendations on the implementation of dose optimization and advice regarding promising strategies that deserve further research in NSCLC.