This chapter reviews the applications of the estimand framework in oncology and hematology, focusing on the unique challenges presented by complex diseases and a variety of treatment options. It stresses the necessity of defining clear trial objectives and establishing reliable estimands to ensure the accurate evaluation of treatment outcomes. Several case studies are included to illustrate the complexities involved in implementing the estimand framework. This chapter highlights how the selection of strategies for the intercurrent events can significantly affect the interpretation of treatment effects and the overall conclusions drawn from the trial. Additionally, it discusses the importance of patient-reported outcomes (PROs) in capturing patients’ perspectives on treatment effects and quality of life while addressing issues related to missing data. The need for alignment between clinical questions and statistical analyses, as outlined in the ICH E9(R1) guideline, is also emphasized. In conclusion, this chapter underscores the vital role of the estimand framework in enhancing the understanding of treatment effects in oncology and hematology, offering insights for researchers and clinicians to navigate the complexities of cancer treatment and improve patient outcomes.