This paper introduces an advanced inventory replenishment optimization approach tailored for the Physical Internet (PI), addressing the dynamic and complex nature of this environment. We propose a hybrid Simulated Annealing–Genetic Algorithm (SA–GA), engineered to optimize the balance between exploration and exploitation, ensuring adaptability and efficiency in a variety of PI contexts. The study also presents an enriched mathematical model integrating dynamic demand, and multi-objective optimization. The SA–GA algorithm emerges as a novel contribution, characterized by its computational efficiency and adaptability, marking an advancement in PI inventory management. The incorporation of real-time data analytics in our dynamic inventory replenishment strategy enhances adaptability and responsiveness, while the robust mathematical model offers a versatile tool for both theoretical analysis and practical application. Collectively, these innovations help bridge existing gaps in PI inventory management and serve as a reference for other similar studies.