Substance abuse has become a major problem in the USA in the past decade, with immense public health and societal consequences. Methamphetamine (meth) use has grown due to an increased number of meth production and distribution markets. Border states such as Arizona and California are especially concerned with Mexico’s production and distribution of meth to their residents. A mathematical model for meth use and markets was developed and then analyzed to track multiple types of drug markets and drug-related arrests for possession or distribution. The importance of social influences as a major causal factor in the onset of illicit drug use is explicitly incorporated. The model parameters are then estimated using meth-related data from California and Arizona. A parameter sensitivity analysis on the model output was carried out. The results suggest that law enforcement policy aimed at marketers will be significantly more effective than targeting current users. Moreover, local unorganized markets have a greater role in maintaining the endemic level of meth users. Whereas, global organized markets play a role in initiating meth use outbreaks. Some implications for interventions and health promotion for the two states are also discussed.