Background: Therapeutic drug monitoring (TDM) consists in measuring and interpreting drug concentrations in biological fluids to personalize drug dosage. This method is widely used for drugs with a narrow therapeutic index (e.g., immunosuppressants or neuroleptics agents). In onco-hematology, current recommendations of TDM for oral molecularly targeted therapies (oMTT) differ among molecules, making it difficult to identify good TDM candidates. This study aims to propose a quantitative approach with a score to predict the clinical usefulness of TDM of oMTT. Methods: We selected the four key parameters needed for an oMTT to be a good candidate for TDM (e.g. interpatient pharmacokinetic variability, feasible dose-adaptation strategy, exposure-efficacy relationship, exposure-safety relationship). We collected each drug’s pharmacokinetic (PK) and pharmacodynamics variables from drug labels, Center for Drug Evaluation and Research reports and early trials data. The score was defined from oMTT’s exposition variability (variability score: coefficient of variation of drug exposition, the impact of food and proton pump inhibitors), technical complexity (PK linearity, active metabolite, half-life), efficacy (Exposure-response relationship (ERR)) and safety (maximum tolerated dose, Exposure-safety relationship (ESR)). The global score ranged from 0 to 100. To assess the relevance of the score, we evaluated molecules from other therapeutic classes with known strong recommendations of TDM (clozapine, everolimus, voriconazole). Results: In September 2021, we collected data from sixty-seven oMTTs. Scores were normally distributed (mean 48.3, standard deviation 15.6) and varies from 15 for acalabrutinib to 80 for sunitinib. Scores of drugs with strong recommendation of TDM were 68, 68 and 64 for clozapine, everolimus as an immunosuppressant, and voriconazole, respectively. We hypothesized that a score above 60 might be associated with relevant indications of TDM. Fifteen molecules had a score above 60 (sunitinib (80), cabozantinib (76.5), nilotinib (76), abemaciclib (76), axitinib (75), sorafenib (69.5) gefitinib (69.5), trametinib (67.5), talazoparib (67), crizotinib (66), pazopanib (65), sonidegib (63.5), neratinib (62.5), panobinostat (62) and imatinib (60.5)). Conclusions: We defined a score to identify good candidates for TDM in onco-hematology. Usefulness of TDM in oncology should be confirmed prospectively prioritizing these molecules.