In the context of increasing complexity in manufacturing and logistic systems, the combination of optimization and simulation can be considered a versatile tool for supporting managerial decision-making. An informed storage location assignment policy is key for improving warehouse operations, which play a vital role in the efficiency of supply chains. Traditional approaches in the literature to solve the storage location assignment problem present some limitations, such as excluding the stochastic variability of processes or the interaction among different warehouse activities. This work addresses those limitations by proposing a discrete-event simheuristic framework that ensures robust solutions in the face of real-life warehouse conditions. The approach followed embraces the complexity of the problem by integrating the order sequence and picking route in the solution construction and uses commercial simulation software to reduce the impact of stochastic events on the quality of the solution. The implementation of this type of novel methodology within a warehouse management system can enhance warehouse efficiency without requiring an increase in automation level. The method developed is tested under a number of computational experiments that show its convenience and point toward future lines of research.