Context: Despite major advancements in the field, the current neurosurgical practice requires an interdisciplinary approach. It is known that surgical practice and other cancer-eliminating treatments can be combined for optimal results. However, recent attempts have failed to address many debilitating conditions, indicating an emergent need for novel interdisciplinary therapeutic approaches. Evidence Acquisition: We searched PubMed and Google Scholar for the keywords “immunoinformatics,” “in silico,” “neurology,” and “neurosurgery.” Without time restriction. Results: The immune system is versatile because it is involved in physiological brain function and affects the course of central nervous system (CNS) disease and infection. A novel approach combines neurosurgery and immunoinformatics for optimal results. For instance, brain tumors, such as glioblastoma multiforme (GBM), are still associated with a severely reduced survival of patients, and resection of tumors may provide little help. In silico approaches could help to identify molecular pathways and design immunotherapies for such conditions at a significantly increased speed compared to traditional vaccinology approaches. Conclusions: The neurosurgical practice could be affected by different infectious organisms. These organisms can be targeted by in silico vaccinology techniques. Here, we provide a brief overview of bioinformatics/immunoinformatics and discuss the possible role of immunoinformatics in neurosurgery. In light of the current Coronavirus disease-2019 (COVID-19) epidemic, projections for future studies are also included.