This epidemiological study assessed the prevalence and risk factors of scrub typhus infection among Particularly Vulnerable Tribal Groups (PVTGs) in Odisha, India. Conducted from June 2022 to May 2023, the community-based survey involved 1,485 participants across nine PVTG-dominated districts. Serum samples were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against scrub typhus using enzyme-linked immunosorbent assay (ELISA) kits. The study found a weighted prevalence of 48.95% for IgG and 18.19% for IgM. Risk factors identified included sitting on muddy floors (adjusted odds ratio [aOR]: 2.00), using non-concrete materials for roofing (aOR: 1.35), engaging in agricultural work (aOR: 1.32), collecting forest resources (aOR: 1.53), childcare (aOR: 1.63), and living in larger households (aOR: 1.27). This research is the first to estimate scrub typhus seroprevalence in this specific community, highlighting the disease’s determinants and recommending enhanced health policies and awareness programs to improve health quality among these marginalized groups.