Glioblastoma is the most common and malignant primary brain tumor, with high morbidity and mortality. Despite an aggressive, multimodal treatment regimen, including surgical resection followed by chemotherapy and radiotherapy, the prognosis of glioblastoma patients remains poor. One formidable challenge to advancing glioblastoma therapy is the complexity of the tumor microenvironment. The tumor microenvironment of glioblastoma is a highly dynamic and heterogeneous system that consists of not only cancerous cells but also various resident or infiltrating inflammatory cells. These inflammatory cells not only provide a unique tumor environment for glioblastoma cells to develop and grow but also play important roles in regulating tumor aggressiveness and treatment resistance. Targeting the tumor microenvironment, especially neuroinflammation, has increasingly been recognized as a novel therapeutic approach in glioblastoma. In this review, we discuss the components of the tumor microenvironment in glioblastoma, focusing on neuroinflammation. We discuss the interactions between different tumor microenvironment components as well as their functions in regulating glioblastoma pathogenesis and progression. We will also discuss the anti-tumor microenvironment interventions that can be employed as potential therapeutic targets.