Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) are common drugs of abuse and driving under their influence may occur in 1 million people yearly in the United States. This systematic review fills the currently unmet need in understanding the effects of METH and MDMA on motor vehicle driving performance (MVP) and provides insight into the forensic community. A PubMed search on September 24, 2020, for experimental and observational studies, which evaluated the impact of METH and MDMA on MVP was performed. After a review of 208 abstracts, 103 were considered potentially interesting and full texts were obtained. After the exclusion of non-English articles, review articles, single case reports, and articles which did not evaluate METH or MDMA on MVP, a total of nine experimental studies, 10 traditional observational studies, and 35 case series were included. The clinical rigor of experimental studies was evaluated using the Jadad scale. Experimental studies often demonstrated no significant MVP safety signals for METH or MDMA use, which was contrary to the overwhelming MVP safety risks found in observational studies. Common driving behaviors while using METH or MDMA include: errors in judgment, traveling at high speeds, failure to stop, merging inappropriately, lane weaving, and crashes. Limitations of experimental studies that led to dissimilar MVP outcomes from observational studies include: the common use of driving simulators, as opposed to actual driving examinations, and doses of METH or MDMA administered may not be representative of blood concentrations seen in observational studies. This systematic review has no funding source and was not registered.