What is known and Objective Sunitinib pharmacokinetics can be influenced by the physio‐pathological conditions of individual patients. Therapeutic drug monitoring (TDM) helps to optimize efficacy and reduce the risk of adverse effects. We report on the use of Bayesian analysis to optimize sunitinib blood levels. Case Summary We describe two patients with risk of sunitinib pharmacokinetic variability due to gastrectomy and ongoing haemodialysis, respectively. TDM and Bayesian estimation allowed maintaining their sunitinib pharmacokinetic profiles within the usual limits. What is new and conclusion Our analysis showed that Bayesian analysis can be successfully applied for real‐time TDM to optimize sunitinib blood levels in patients with major comorbidities.