Grant McFadden's work focuses on vaccines, immunology, and understanding how a virus evades the immune system of its host. He developed the field of viral immune subversion, and focuses on poxviruses, looking into creating a virus that attacks cancer cells. Professor McFadden is working to apply his work toward virotherapy and improve stem cell blood transfusions. He is in the process of human trials, utilizing the myxoma virus for his novel virotherapy techniques.

McFadden is the director for Biodesign Center for Immunotherapy, Vaccines and Virotherapy, and contributes to the Center for Evolution and Medicine. He is also a division leader for the Well-being commons.

McFadden is a committee member for ICTV and the World Health Organization Advisory Committee on Variola Virus Research. He collaborate with the University of Florida. McFAdden is on the editorial boards for Oncolytic Virotherapy, J. Virology, PLoS Pathogens, and Molecular Therapy-Oncolytics.