A rapidly developing field of study is immunomodulation, which is employed to treat diseases such as cancer and autoimmune disorders. It is possible to create nanofibers with improved immunomodulatory effectiveness and precisely targeted delivery for modifying the immune system. In this instance, we go into detail about numerous strategies that use nanotechnologies, like carbon nanofibers, inorganic nanofibers, organic nanofibers and we go over their sophisticated construction, workings, and purposes. Targeting immunological organs or cells and regulating releasing rates using this kind of nanotechnology engineering could advance existing technological boundaries and offer fresh, creative treatments for illnesses and immune-related disorders without having any undesirable side effects. Fibrous nanomaterials' better integrated structure, biological compatibility, flexible magnitude, and selective surface alterations have recently enabled advancements in tissue regeneration and therapies for cancer. The nanofibers based on immunoactivation may be able to actively support immunologic intervention by delivering active substances to wounds. Instead, by restricting important pathways in vivo, the immunosuppression-based nanofibers prohibit the body's defenses from reacting. This chapter outlines the present use of nanofiber materials in a variety of disorders, such as organ defects, cardiac infarction, dermatitis, cancer therapies, and reconstruction of tissues. In the meantime, the current technical obstacles and viewpoints are logically examined, offering helpful motivation for the subsequent fundamental studies and clinical development of nanofibers in the dynamic biomedical domains. By emphasizing safety, personalization, and adherence to legal requirements, these technologies can dramatically advance precision medicine and change the healthcare industry.