Chemicals are listed on California’s Proposition 65 (Prop 65) for their potential to cause cancer, birth defects or other reproductive harm, and certain chemicals from this list are often detected within interior vehicle dust and air. Therefore, this study examined the potential risk associated with five Prop 65-listed chemicals detected within vehicle interiors: benzene, formaldehyde, di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and tris(1,3-dichloro-2-propyl)phosphate (TDCIPP). Exposure estimates based on time spent within a vehicle were derived from a meta-analysis of estimated concentrations from the literature. Regulatory levels established by the California Office of Environmental Health Hazard Assessment (OEHHA) were then used to generate percent reference doses (%RfDs) for chemical-specific daily doses as well as determine the probability of risk (exceedance probability) as a function of %RfD for each chemical-specific daily dose. Based on our meta-analysis, benzene and formaldehyde were detected in vehicle interior air whereas DEHP, DBP and TDCIPP were detected in vehicle interior dust. Benzene and formaldehyde were the only two chemicals with an estimated %RfD > 100 across any of the commute times. For commute times of 20 min or longer, the %RfD was > 100 for maximum exposures based on the “maximum allowable daily level” for benzene, and for 95th-percentile exposures based on the “no significant risk level” for benzene and formaldehyde. Furthermore, the probability of exceeding 100% RfD was highest for cancer risks associated with benzene, followed by cancer risks associated with formaldehyde and the risk of reproductive and developmental toxicity associated with benzene. Lastly, within the entire state of California, the percent of commuters with a 10% probability of exceeding cancer risk associated with benzene or formaldehyde exposure was 78% and 63%, respectively. Overall, our study raises concerns about the potential risk associated with inhalation of benzene and formaldehyde for people who spend a significant amount of time in their vehicles, an issue that is especially pertinent to traffic-congested areas where people have longer commutes.