Prescription drug expenditures and utilization are the fastest growing and most widely varying expenditures within Medicaid programs across US states. The passage of the Affordable Care Act (ACA) in 2010 and the subsequent Medicaid state expansions resulted in very large coverage gains among several demographics. Prior to the ACA a number of studies highlighting determinants of overall healthcare utilization and expenditures had been undertaken. Most of these studies examined discreet determinants for overall health care. However, these determinants, their interactions have not been tested concurrently in relation to pharmaceutical expenditures. Data from the Centers for Medicare and Medicaid Services (CMS), US Department of Labor, Department of Education, and state Medicaid programs were merged to create a balanced panel data (n=350 observations and 53 variables over a seven (7) period from 2009 to 2015). Based on Andersen’s Behavioral Model of Health Services, and using STATA-16, a random effects (RE) panel regression analysis is undertaken to estimate an econometric model for Medicaid pharmaceutical expenditures. A Partial Least Square-Structural Equation Model is developed to examine the relationships between and test the hypothesized effects of policy, access and predisposing factors on State Medicaid expenditures. The model estimate showed a significant influence on drug expenditures of state non-drug Medicaid expenditures, proportion of males in the population, and provider education programs on generics. Discussions, limitations and future directions for research are stated