Recently, oncological pharmacotherapy and the related imaging and laboratory techniques employed for the optimization and monitoring of interventions have undergone revolutionary development. The implementation of personalized treatments based on therapeutic drug monitoring (TDM) is, with a few exceptions, lacking. The key factor limiting the integration of TDM into oncological practice is the need for dedicated central laboratories with resource-intensive, specialized analytical instruments, as well as highly skilled multidisciplinary staff. Unlike in certain other fields, the monitoring of serum trough concentrations often fails to provide clinically relevant information. Instead, the clinical interpretation of the results requires clinical pharmacological and bioinformatics expertise. Our goal is to present the pharmacokinetic-pharmacodynamic considerations of interpreting oncological TDM assay outcomes with the aim of providing direct support for clinical decision making.