Aims: The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients is quite different. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of various biological covariates and the use of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Methods: The modeling analysis of the pharmacokinetic parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) using a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. Results: A total of 408 critically ill patients with 746 voriconazole concentration–time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CLCR), platelet (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. Conclusion: The results showed that qCRP, CRRT, CLCR, PLT, and PT affected the PK parameter clearance. The most commonly used clinical regimen of 200 mg q12h is sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L) in China, regardless of whether CRRT is performed, and at what level qCRP is. When the MIC is 0.5 mg/L, 200 mg q12h is insufficient only when qCRP is less than 40 mg/L and CRRT is performed. When MIC ≥ 2 mg /L, a dose of 300 mg q12h cannot achieve ≥ 90% PTA, and a higher dose needs to be explored.