Nadolol has demonstrated its superior efficacy over other β-blockers in the treatment of specific cardiovascular diseases in children. The clinical development of nadolol for pediatric use was prioritized by Chinese healthcare authorities in May 2023 while there was a lack of clear medication instructions for children. To expedite the pediatric development of nadolol and provide insights into its off-label applications, we developed a physiologically based pharmacokinetic model incorporating mechanistic disposition knowledge. This model integrates key processes of nadolol including P-glycoprotein (P-gp) transporter mediated the absorption of efflux, multidrug and toxin extrusion protein (MATE) 1 transporter and organic cation (OCT) 2 transporter mediated active renal excretion, organic anion transporting polypeptide (OATP) 1A2 mediated transport, along with biliary excretion. The model accurately captured the pharmacokinetic profiles of nadolol in both Western and East Asian populations following a wide dose range (2-160 mg), including the plasma concentration, urine excretion, and drug-drug interactions with the P-gp inhibitor. After our good validation on interracial adult populations, simulations of nadolol pharmacokinetic profiles in the Chinese population were performed by adjusting the liver volume of the Chinese to 0.9 of the Japanese population. Then, with the consideration of physiological changes and plasma protein ontogeny in pediatrics, the nadolol model for pediatrics was also well-verified on several children aged 3 months to 121 months. Accordingly, specific optimal dosages for children across various ages and racial backgrounds with or without obesity were offered by exposure matching with adults. Multiple remedial regimen simulations were also compared to obtain the best nonadherence management in the case of missed dosages, in which resuming a regular dose as soon as possible was the most recommended.