In cancer therapy, cognitive impairment is a significant concern, especially in treatments that target the central nervous system (CNS). People with brain tumors, particularly those who have been treated in the past, commonly suffer from cognitive impairments, including executive function, memory, attention, and social skills. The impact of immunotherapy on cognition has been questioned regarding its potential for treating CNS cancer. Cognitive impairment is a significant concern in cancer therapy, particularly in treatments targeting the CNS. Specifically, this chapter summarizes the complex relationship between cancer therapy that targets the CNS and cognitive impairment. In addition, it explores the influences on cognitive features in CNS-related tumors and the immunotherapy participation in CNS-related cancer therapy. During CNS cancer treatment, potential risk factors and mitigating strategies for cognitive impairment are also discussed, offering insight into care and optimizing the quality of life in affected patients.