Histoplasmosis is an airborne systemic infection, with varied clinical manifestations, from asymptomatic infection to disseminated disease with a deadly outcome. Due to a growing number of immunosuppressed people, this mycosis has become more prevalent and thus, a cause for concern within the medical community. In fact, this fungal infection can be quite serious for children, elderly, people who have had an organ transplant, HIV-positive or people taking immunosuppressants. There has been a limited number of research articles suggesting polymeric, metallic, or lipid micro and nanotechnology-based approaches as a potential way to carry antifungal drugs to treat histoplasmosis. These new drug delivery systems present a variety of means of administration, thereby allowing a more targeted treatment to the lungs, skin, or eyes, according to the infection site. In this review, the aim was to explore these new therapies that have been emerging which hold great potential in comparison to regular antifungal treatments, not only due to their safety but also due to their drug release profile.