In this study, a methodology for optimal sizing of waste heat recovery (WHR) systems is presented. It deals with dynamic engine conditions. This study focuses on Euro-VI truck applications with a mechanically coupled Organic Rankine Cycle-based WHR system. An alternating optimization architecture is developed for optimal system sizing and control of the WHR system. The sizing problem is formulated as a fuel consumption and system cost optimization problem using a newly developed, scalable WHR system model. Constraints related to safe WHR operation and system mass are included in this methodology. The components scaled in this study are the expander and the EGR and exhaust gas evaporators. The WHR system size is optimized over a hot World Harmonized Transient Cycle (WHTC), which consists of urban, rural and highway driving conditions. The optimal component sizes are found to vary for these different driving conditions. By implementing a switching model predictive control (MPC) strategy on the optimally sized WHR system, its performance is validated. The net fuel consumption is found to be reduced by 1.1% as compared to the originally sized WHR system over the total WHTC.