Background: Occupational use of pyrethroid insecticides indoors remains widespread due to their effectiveness and perceived safety compared with older pesticide classes. However, enclosed workplaces with central heating, ventilation, and air-conditioning (HVAC) systems—especially those with wall-to-wall carpeting and dust-accumulating surfaces—can sustain residue persistence and repeated low-dose exposure far beyond the spray event. No evidence-based or standardized guidelines currently define safe spray-ing frequency, residue decay intervals, or ventilation requirements for such environ-ments, representing a major regulatory and research gap; Objective: This review intro-duces the concept of the occupational indoor pyrethroid exposome—the cumulative exposure environment created by recurrent spraying, residue persistence, and resuspension—and identifies mechanistic links to thyroid, neurological, cardiovascular, hepatic, and immune toxicity; Methods: A structured literature review was conducted across biomedical and environmental databases. Included studies addressed (i) indoor pyrethroid use and resi-due persistence in dust or surfaces; (ii) resuspension and HVAC-mediated redistribution; (iii) human biomonitoring and health outcomes; and (iv) mechanistic data related to en-docrine, hepatic, neurological, cardiovascular, and immune effects. Only peer-reviewed studies were analyzed; Results: Evidence shows that pyrethroid residues persist in indoor dust and textile reservoirs, leading to chronic, low-dose exposure through resuspension and contact transfer. Mechanistic findings indicate that voltage-gated sodium channel modulation, mitochondrial dysfunction, oxidative stress, and inflammatory signaling act as convergent pathways linking chronic exposure to neuroexcitation, endocrine disrup-tion, hepatic enzyme induction, vascular dysfunction, and immune dysregulation. Limited occupational data highlight a consistent association between long-term indoor spraying and elevated biomarkers of hepatic and thyroid stress; Conclusions: The absence of clear occupational safety standards for indoor pyrethroid use constitutes a major gap in pesti-cide regulation and workplace health protection. Integrating residue monitoring, ventila-tion assessment, and mechanistic biomarkers into occupational risk frameworks is essen-tial to guide safe spraying intervals, improve exposure surveillance, and prevent chronic multisystem toxicity among workers in enclosed environments. This framework not only supports the development of evidence-based occupational pesticide safety standards and improved ventilation policies in enclosed workplaces, but also highlights a critical regu-latory gap — the current absence of any evidence-based guidelines defining safe frequen-cy or interval for indoor pyrethroid spraying.