Blood transfusion is one of the most crucial and commonly administered therapeutics worldwide. The need for more accurate and efficient ways to manage blood demand and supply is an increasing concern. Building a technology-based, robust blood demand and supply chain that can achieve the goals of reducing ordering frequency, inventory level, wastage and shortage, while maintaining the safety of blood usage, is essential in modern healthcare systems. In this study, we summarize the key challenges in current demand and supply management for red blood cells (RBCs). We combine ideas from statistical time series modeling, machine learning, and operations research in developing an ordering decision strategy for RBCs, through integrating a hybrid demand forecasting model using clinical predictors and a data-driven multi-period inventory problem considering inventory and reorder constraints. We have applied the integrated ordering strategy to the blood inventory management system in Hamilton, Ontario using a large clinical database from 2008 to 2018. The proposed hybrid demand forecasting model provides robust and accurate predictions, and identifies important clinical predictors for short-term RBC demand forecasting. Compared with the actual historical data, our integrated ordering strategy reduces the inventory level by 40% and decreases the ordering frequency by 60%, with low incidence of shortages and wastage due to expiration. If implemented successfully, our proposed strategy can achieve significant cost savings for healthcare systems and blood suppliers. The proposed ordering strategy is generalizable to other blood products or even other perishable products.