In the United States, nicotine is the most used drug by pregnant women. It has been well established that prenatal nicotine can cross the placental barrier and alter behavioral development. Unfortunately, many pregnant women combine nicotine consumption with other drugs, such as cannabis. Little is known of the effects of maternal cannabis use on the developing fetus, alone or in combination with nicotine. Furthermore, the use of electronic cigarettes (e-cigarettes) is rising among pregnant women because they believe that it is safer than smoking a traditional cigarette. Thus, the present study used a rodent model to examine how e-cigarette exposure to prenatal nicotine, THC, and the combination impacts motor coordination in rodent offspring. Pregnant Sprague-Dawley (n = 48) rats were exposed to nicotine, THC, the combination, or vehicle (propylene glycol) via vapor inhalation (e-cigarettes) from gestational days (GD) 5-20. A vapor inhalation system was used to administer 36 mg/mL nicotine, 100 mg/mL THC, the combination or vehicle via an e-cigarette. On GD 5-20, pregnant dams were placed in vapor chambers for 40 minutes and e-cigarettes were added into the airflow in 6-second puffs every 5 minutes. The offspring (one male and female from each litter) from PD 30-32 (equivalent to human adolescence), were tested on a motor coordination task. Prenatal nicotine and/or THC exposure via e-cigarette impaired motor performance. Offspring that were prenatally exposed to nicotine or THC were less successful at completing the parallel bar task compared to offspring that were not prenatally exposed to drug. Additionally, when offspring were exposed to the combination of nicotine and THC, this caused further impairments in offspring compared to either drug alone. Lastly, these effects were more robust in females on one outcome measure. This study illustrates that either prenatal nicotine and/or THC exposure via an e-cigarette can impair motor development and that the combination produces more severe motor deficits. In conclusion, these results suggest that e-cigarette usage during pregnancy is not safe, especially with polydrug use. These findings have important implications for pregnant women and understanding the teratogenic effects of these drugs via newer routes of administration.