Background: Glioblastoma is a grade IV astrocytoma with an average survival span for patients of 18 months after initial diagnosis and no standard treatment protocol. There is a need to look at novel approaches to target glioblastoma. Objectives: This review intends to capture the role of immunoglobulin-M in cancer, more specifically in glioblastoma multiforme (GBM), and to compile the latest developments and immunological pathways relevant to glioblastoma Methods: Information on glioblastoma, cancer microenvironment, cancer therapeutics and how to improve the scenario was obtained from scientific literature databases such as Pubmed, Medline, Google Scholar, Science Direct, Springer, Wiley online library and some data was harvested from regulatory and compliance databases such as clinicaltrials.gov, FDA database, WHO Globocan. Results and Conclusions: Currently, only a limited number of therapies are approved for GBM, and no standard of care is in place in case of disease relapse, necessitating a possible broader perspective in looking at the disease and its underlying mechanisms.