Exercise has been increasingly recognized in clinical guidelines as a recommended component of rehabilitation for people with hemophilia (PWH), with evidence supporting appropriate physical activity’s multifaceted benefits. During exercise, the bleeding risk in PWH exhibits a critical correlation with circulating clotting factor activities, where higher factor concentrations demonstrably reduce hemorrhagic events. However, economic constraints limit universal access to high-dose prophylactic clotting factor replacement therapy. Through pharmacokinetics (PK) monitoring of clotting factor, clinicians can strategically tailor exercise types and frequencies, or adjust factor replacement dosages based on activity-specific demands. This individualized approach not only enhances the cost-effectiveness of clotting factor utilization, but also improves safety by mitigating bleeding risks. This article examines the feasibility and recent advancements in PK-guided individualized physical activity prescriptions for PWH, presenting evidence-based insights to inform clinical practice and future research priorities.