Aim: The study aimed to establish a population pharmacokinetic (PPK) model for Chinese patients with nephrotic syndrome using the patient genotype and Wuzhi capsule dose as the main test factors. Methods: Adult patients with nephrotic syndrome receiving tacrolimus treatment were enrolled. A nonlinear mixed effects model was used to determine the influencing factors of inter-individual tacrolimus metabolism variation and establish a PPK model. To optimize the tacrolimus dosage, 10000 Monte Carlo simulations were performed. Results: The typical population tacrolimus clearance (CL/F) value was 16.9 L/h. Increased Wuzhi capsule and albumin doses both decreased the tacrolimus CL/F. In CYP3A5 homozygous mutation carriers; the CL/F was 39% lower than that of carriers of the wild-type and heterozygous mutation. The tacrolimus CL/F in patients who were co-administered glucocorticoids was 1.23-fold higher than that in the control. According to the patient genotype and combined use of glucocorticoids, 26 combinations of Wuzhi capsule and tacrolimus doses were matched. The Monte Carlo simulation identified the most suitable combination scheme. Conclusion: An improved tacrolimus PPK model for patients with nephrotic syndrome was established and the most suitable combination of Wuzhi capsule and tacrolimus doses was identified, thus facilitating the selection of a more economical and safe administration regimen.