Aims: Olanzapine, a second-generation antipsychotic, can cause dose-adverse drug reactions. Its steady-state concentration can vary due to several factors. This study explores how physiological factors, smoking, inflammation, concomitant medications, and metabolic enzyme single nucleotide polymorphisms (SNPs) influence its metabolic levels, aiming to guide personalized dosing. Methods: This study analyzed data from 310 olanzapine-treated patients at Beijing Anding Hospital. Liquid chromatography-mass spectrometry (LC-MS/MS) quantified 1002 serum concentrations. Eleven SNPs from CYP1A2, CYP3A5, UGT1A4, and FMO1/3 were identified through real-time fluorescence quantitative polymerase chain reaction (q-PCR). A Bayesian network was applied to elucidate causal relationships between variables, followed by g-computation to quantify the effect of individual factors on the dose-adjusted concentration (C/D ratio) of olanzapine. The Wilcoxon signed-rank test assessed the intra-individual variations in the steady-state C/D ratio. Results: The Bayesian network suggested causality between smoking, sex, sertraline, Danggui-Longhui, valproic acid, and the olanzapine C/D ratio. None of the SNPs reached significance levels. The Wilcoxon signed-rank test confirmed that both polypharmacy and inflammation increased the C/D ratio within individuals. G-computation showed that the log ratio of olanzapine C/D decreased by 0.392 ± 0.037 in males and 0.004 ± 0.001 with smoking. Danggui-Longhui, sertraline, and valproic acid reduced the ratio by 0.652 ± 0.131, 0.398 ± 0.127, and 0.328 ± 0.039, respectively. Conclusion: Our study confirms that sex, age, smoking, inflammation, and co-prescription with sertraline, Danggui-Longhui, and valproic acid contributed to variability in olanzapine’s steady-state concentration. Considering these factors in clinical practice may help to personalize olanzapine treatment in Asian patients.