Primary brain tumors represent a significant focus of contemporary research. With advancements in technology and the increasing detection of cases through novel diagnostic methods, innovative therapies and approaches to chemotherapy continue to emerge. The paper explores recent advancements in chemotherapy for glioblastoma, highlighting innovative approaches that provide valuable mechanistic insights. It delves into the mechanisms of action, molecular targets, and the future potential of emerging therapies for gliomas. Additionally, this paper offers an overview investigating a range of therapies, including various chemotherapeutic agents, CAR-T cell therapies, drugs targeting cellular respiration, and other approaches. Furthermore, the paper addresses chemotherapy-related challenges, including the blood-brain barrier, drug resistance, and immunosuppression, while proposing potential solutions to overcome these obstacles.