Glioblastoma (GB) is a highly aggressive and invasive tumor of the central nervous system (CNS) with a five-year survival rate of 6.9% and a median survival time of eight months. Despite treatment with surgery, radiotherapy, and chemotherapy, recurrence is common, often occurring at the edge of the resection cavity. The peritumoral brain zone (PBZ) is a critical area surrounding the tumor that plays a significant role in GB progression, recurrence, and resistance to therapy. This review summarizes the biological, clinical, and mechanical features of the PBZ, highlighting its complex interactions with GB cells and the tumor microenvironment. The PBZ is defined by molecular, radiological, and cellular alterations that promote GB cell proliferation, invasion, and recurrence. Radiologically, the PBZ is characterized by a lack of contrast enhancement in T1 gadolinium-enhanced MRI, but this does not necessarily indicate the absence of tumor cells. Histologically, the PBZ resembles normal brain tissue, but few studies have explored its cellular and molecular characteristics. The PBZ is influenced by the tumor bulk, making it distinct from normal brain tissue and closer to the tumor core. The PBZ contains a diverse population of GB cells, including GB stem-like cells (GSCs), which are capable of self-renewal and differentiation into non-stem GB cells. These GSCs exhibit varying stemness and are found in different niches within the tumor core and PBZ, contributing to GB progression and therapeutic resistance. The PBZ is also characterized by a unique cell spatial heterogeneity, with distinct cellular states such as mesenchymal-like (MES-like), astrocyte-like (AC-like), and neural progenitor-like (NPC-like) cells. These states are influenced by factors such as CD133 and CD109 expression, which are associated with different GB subtypes. The PBZ is also influenced by the mechanical properties of the tumor and surrounding tissue, including interstitial fluid pressure (IFP), solid stress, and ECM stiffness. These mechanical factors affect GB cell behavior, including proliferation, invasion, and resistance to therapy. The PBZ is a dynamic environment that interacts with the tumor microenvironment, contributing to GB progression and recurrence. The PBZ is also a critical area for immune cell interactions, with tumor-associated macrophages (TAMs) and microglia playing a significant role in GB progression and resistance to therapy. The PBZ contains a higher number of effector T-cells that are not exhausted, while the tumor core is more immunosuppressive and contains more Tregs and exhausted CD8+ T cells. The PBZ is also characterized by a unique immune microenvironment that may be more favorable for immunotherapy. The PBZ is a complex and dynamic area that plays a critical role in GB progression, recurrence, and resistance to therapy. Understanding the biological, clinical, and mechanical features ofGlioblastoma (GB) is a highly aggressive and invasive tumor of the central nervous system (CNS) with a five-year survival rate of 6.9% and a median survival time of eight months. Despite treatment with surgery, radiotherapy, and chemotherapy, recurrence is common, often occurring at the edge of the resection cavity. The peritumoral brain zone (PBZ) is a critical area surrounding the tumor that plays a significant role in GB progression, recurrence, and resistance to therapy. This review summarizes the biological, clinical, and mechanical features of the PBZ, highlighting its complex interactions with GB cells and the tumor microenvironment. The PBZ is defined by molecular, radiological, and cellular alterations that promote GB cell proliferation, invasion, and recurrence. Radiologically, the PBZ is characterized by a lack of contrast enhancement in T1 gadolinium-enhanced MRI, but this does not necessarily indicate the absence of tumor cells. Histologically, the PBZ resembles normal brain tissue, but few studies have explored its cellular and molecular characteristics. The PBZ is influenced by the tumor bulk, making it distinct from normal brain tissue and closer to the tumor core. The PBZ contains a diverse population of GB cells, including GB stem-like cells (GSCs), which are capable of self-renewal and differentiation into non-stem GB cells. These GSCs exhibit varying stemness and are found in different niches within the tumor core and PBZ, contributing to GB progression and therapeutic resistance. The PBZ is also characterized by a unique cell spatial heterogeneity, with distinct cellular states such as mesenchymal-like (MES-like), astrocyte-like (AC-like), and neural progenitor-like (NPC-like) cells. These states are influenced by factors such as CD133 and CD109 expression, which are associated with different GB subtypes. The PBZ is also influenced by the mechanical properties of the tumor and surrounding tissue, including interstitial fluid pressure (IFP), solid stress, and ECM stiffness. These mechanical factors affect GB cell behavior, including proliferation, invasion, and resistance to therapy. The PBZ is a dynamic environment that interacts with the tumor microenvironment, contributing to GB progression and recurrence. The PBZ is also a critical area for immune cell interactions, with tumor-associated macrophages (TAMs) and microglia playing a significant role in GB progression and resistance to therapy. The PBZ contains a higher number of effector T-cells that are not exhausted, while the tumor core is more immunosuppressive and contains more Tregs and exhausted CD8+ T cells. The PBZ is also characterized by a unique immune microenvironment that may be more favorable for immunotherapy. The PBZ is a complex and dynamic area that plays a critical role in GB progression, recurrence, and resistance to therapy. Understanding the biological, clinical, and mechanical features of