PFAS are known contaminants of indoor dust. Despite the adherence of such dust to skin, the dermal penetration potential of PFAS is not well understood. By applying in vitro physiologically based extraction tests, the bioaccessibility of 17 PFAS from indoor dust to synthetic human sweat sebum mixtures (SSSM) was assessed. The composition of the SSSM substantially impacted the bioaccessibility of all target compounds. PFAS bioaccessibility in a 1:1 sweat:sebum mixture ranged from 54 to 92% for perfluorocarboxylic acids (PFCAs) and 61–77% for perfluorosulfonic acids (PFSAs). Commonly applied cosmetics (foundation, sunscreen, moisturiser, and deodorant) significantly impacted the dermal bioaccessibility of target PFAS, e.g., the presence of moisturiser significantly decreased the total bioaccessibility of both PFCAs and PFSAs. Preliminary human exposure estimates revealed dermal contact with indoor dust could contribute as much as pathways such as drinking water and dust ingestion to an adult’s daily intake of PFAS. While further research is needed to assess the percutaneous penetration of PFAS in humans, the current study highlights the potential substantial contribution of dermal exposure to human body burdens of PFAS and the need for further consideration of this pathway in PFAS risk assessment studies.