In our previous work, molecular dynamics simulation was used to calculate Young’s modulus of both fully and partially exfoliated effective clay (montmorillonite, MMT) clusters. In this work, we expand that work to predict the overall Young’s moduli of nylon 6/MMT nanocomposites. First, a micromechanics method (i.e. the rule-of-mixtures) is shown to be effective in calculating the overall Young’s moduli of clay-based polymer nanocomposites. Then, the overall Young’s moduli of clay-based polymer nanocomposites with either well-aligned or randomly dispersed effective clay clusters of various clay volume fractions are calculated based on the individual Young’s moduli of effective clay clusters and polymer matrix by the rule-of-mixtures method. By comparing the simulated results with measured data in the literature, it is shown that the present approach provides an effective way to predict the overall Young’s moduli of nylon 6/MMT nanocomposites.