A clear and systematic understanding of the drug's in vivo performance leading to the bioavailability of the drug substance is of paramount importance in drug design, development, medical applications, and toxicity evaluation. In contrast to the conventional injectable solution dosage forms, the intravenous nano-Drug Delivery Systems (DDS) are divided into two parts: free and encapsulated drugs. The encapsulated drug is the key to improving release and distribution in vivo. However, researching the pharmacokinetics (PK) and pharmacodynamics (PD) of the nano-drug delivery system using the classical compartment models for traditional solution dosage forms is problematic in that the encapsulated and free drugs are co-existent, thus warranting more consideration in the nano-drug delivery system. In this paper, we proposed a novel approach of modeling PK and PK-PD's “linear multiple input and single output system” for intravenous nano-drug delivery system, which can accurately predict the velocity and distribution of free-drug and encapsulated-drug. The new approach will play a great role in facilitating the development of scutellarin emulsion as the model of drug delivery system, providing insight into the clinical translation of nano-medicine, and shedding some light on the future of precision medicine and personalized medicine.