Glioblastoma (GBM) is an aggressive form of brain cancer with very little treatments. Exploring the tumor microenvironment allows for better understanding of cancer cell survival and the network of cells. Hyaluronic acid is an important component of the extracellular matrix. Hypoxic environments are associated with extracellular matrix remodeling and increased metastatic behavior. While exploring the tumor microenvironment, the objective of this research was to examine how hypoxia effects hyaluronic acid synthesis in glioblastoma influencing its metabolism and efficacy of drug therapies by manipulating cell encapsulated hydrogels. The hydrogels were treated with hyaluronic acid, Erlotinib, and Glycyrrhizic acid. The hydrogels were stained and imaged with clear indication of hypoxic effects on HA production. From the results, HA production was significant when tumor microenvironment was stressed with hypoxia. These findings help to explore how HA production is affecting the GBM tumor microenvironment.