Abstract: Objective To systematically synthesize evidence on multiple KRAS G12C inhibitors (KRAS G12C inhibitors, KRAS G12Ci) as monotherapy within a unified population and recommended-dose framework, establish a comparable benchmark range of efficacy and safety for previously treated patients with advanced or metastatic KRAS G12C-mutant non-small cell lung cancer (NSCLC), and explore potential effect modifiers. Methods We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov, and major international conference abstracts, and included clinical-trial cohorts enrolling patients with advanced or metastatic KRAS G12C-mutant NSCLC who were G12Ci-naïve and received recommended-dose G12Ci monotherapy. Random-effects models were used to pool objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and the incidence of any-grade and grade ≥3 treatment-related adverse events (TRAEs). For biomarker stratification, pooled odds ratios (OR) were calculated to assess associations between co-mutations and programmed death-ligand 1 expression and ORR. Results The single-arm meta-analysis included 11 independent study cohorts. The pooled ORR using a random-effects model was 44% (95% CI: 38%–49%) and the pooled DCR was 86% (95% CI: 82%– 88%). The pooled mPFS was 7.70 months (95% CI: 5.82–10.20) and the pooled mOS was 12.63 months (95% CI: 10.07–15.83). For safety, the pooled incidence of any-grade TRAEs was 92% (95% CI: 86%–96%), and grade ≥3 TRAEs was 39% (95% CI: 33%–45%). The toxicity profile was dominated by hepatobiliary laboratory abnormalities, renal dysfunction/proteinuria, and gastrointestinal events. Exploratory stratified analyses suggested that KEAP1 co-mutation was significantly associated with a lower ORR (OR=0.37, 95% CI: 0.21–0.65); no significant stratification effect was observed for TP53 co-mutation or PD-L1 expression (at 1% and 50% cutoffs); and the association between STK11 co-mutation and ORR did not reach statistical significance (OR=0.63, 95% CI: 0.37–1.08). Conclusion In previously treated patients with advanced KRAS G12C-mutant NSCLC, KRAS G12Ci monotherapy achieves stable overall response rates and disease control rates, yielding an efficacy and safety benchmark range that may facilitate clinical interpretation and cross-study comparisons. During treatment, standardized monitoring of hepatobiliary biochemistry, renal function, proteinuria, and gastrointestinal toxicities should be emphasized. Exploratory evidence indicates that KEAP1 co-mutation may represent a more actionable negative stratification signal.