Summary: For a drifted Multiple-Input and Multiple-Output (MIMO) system, the double Multivariate Exponentially Weighted Moving Average (dMEWMA) controller is a popular run-to-run controller for adjusting the process mean to a desired target. The stability and performance of dMEWMA controller had been widely studied in literature. Although the dMEWMA controller (with suitable discount matrices) can guarantee long-term stability, it usually requires a moderately large number of runs to bring the process output to approach its desired target if the initial recipe is not chosen appropriately. Due to the initial recipe possibly having an infinite number of feasible solutions for MIMO systems, “how to determine an optimal setting for the initial recipe” turns out to be an interesting research topic. In this article, by solving a constrained optimization problem, we first obtain an optimal initial setting for the input recipe. Then, motivated by this setting, we propose an enhanced dMEWMA controller. The long-term stability conditions and short-term performance of the proposed controller are also addressed. Given a fixed and finite production run, it reveals that the proposed controller has the ability of reducing the total mean squared error better than the conventional dMEWMA controller.