Gliomas are highly invasive brain tumors with poor prognosis, primarily due to their ability to infiltrate surrounding brain tissue and recur after surgical removal. This review explores the molecular and cellular mechanisms underlying glioma invasion, focusing on intrinsic drivers such as tumor cell interactions and the tumor microenvironment (TME). Key mechanisms include the formation of tumor microtubes (TMs) and tunneling nanotubes (TNTs), which facilitate communication and invasion. The neuronal niche, including local and distant neurons, plays a crucial role in glioma growth and invasion. Astrocytes and immune cells also contribute to glioma invasion through various mechanisms, such as releasing growth factors and promoting ECM remodeling. Therapeutic strategies targeting these mechanisms, including gap junction inhibitors, microtubule-targeting agents, and neurotrophic factor inhibitors, are discussed. The review highlights the importance of understanding these mechanisms for developing effective treatments to combat glioma invasion and improve patient outcomes.Gliomas are highly invasive brain tumors with poor prognosis, primarily due to their ability to infiltrate surrounding brain tissue and recur after surgical removal. This review explores the molecular and cellular mechanisms underlying glioma invasion, focusing on intrinsic drivers such as tumor cell interactions and the tumor microenvironment (TME). Key mechanisms include the formation of tumor microtubes (TMs) and tunneling nanotubes (TNTs), which facilitate communication and invasion. The neuronal niche, including local and distant neurons, plays a crucial role in glioma growth and invasion. Astrocytes and immune cells also contribute to glioma invasion through various mechanisms, such as releasing growth factors and promoting ECM remodeling. Therapeutic strategies targeting these mechanisms, including gap junction inhibitors, microtubule-targeting agents, and neurotrophic factor inhibitors, are discussed. The review highlights the importance of understanding these mechanisms for developing effective treatments to combat glioma invasion and improve patient outcomes.