Aim: In this study, a population pharmacokinetic (PPK) model for imipenem was developed specifically for patients with febrile neutropenia 189 out of 250 words(FN) and hematological malignancies, with the aim of identifying optimal pharmacokinetic/pharmacodynamic (PK/PD) targets to predict antimicrobial efficacy and guide dosing regimens. Methods: A prospective, single-center, open-label study was conducted, analyzing 207 plasma samples from 121 Chinese patients with FN and hematological malignancies using chromatography. Pharmacokinetic parameters were evaluated using NONMEM to analyze the relationship between drug clearance and various patient-specific covariates. Results and conclusion: The analysis revealed that drug clearance was significantly impacted by creatinine clearance (CLCR), gamma-glutamyltransferase (GGT), and vancomycin (VAN) co-administration. The final PPK model was defined as follows: CL (L·h-1) = 21.36 × (CLCR/110.39)0.444 × (GGT/55.4)-0.119 + VAN × 3.78; central compartment volume (L) = 42.9; intercompartmental clearance (L·h-1) = 3.7; and peripheral compartment volume (L) = 59. The optimal PK/PD target for predicting imipenem’s antibacterial efficacy was determined to be an f%T > MIC of 90.48%. Therefore, dosing adjustments should account for CLCR, GGT levels, and VAN co-administration. For patients with infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii, additional antimicrobial agents are recommended when necessary.