Aims and Objectives: The prognostic value of nutritional status in HR+/HER2- metastatic breast cancer (mBC) patients treated with CDK4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is unclear. Methods/Materials: The effect of PNI values before starting CDK 4/6i on patient prognosis was retrospectively analyzed. Results: A total of 431 patients were evaluated. After 35.7 months of follow-up, the median overall survival (mOS) was 46.3 months (95% CI, 29.7–62.8). The PNI-low group had decreased progression-free survival compared to the PNI-high group [16.6 vs. 30.5 months; univariate HR = 1.640, 95% confidence interval (CI): 1.281–2.099, P < .001]. The PNI-low group's mOS was noticeably shorter than the PNI-high group (35.0 months vs. not reached; multivariate-adjusted HR: 2.082, 95% CI: 1.398–3.102, P < .001). When stratified by CDK4/6i line: In patients using CDK4/6i as the first line, mPFS for the PNI-low and PNI-high group was 24.6 vs. 35.6 months (P = .026), and survival probabilities at 24, 36, and 48 months in the PNI-low and PNI-high groups were 75%, 62%, 57%, and 88%, 80%, and 72%, respectively (P = .002). In patients using CDK4/6i as the second line and after, mPFS was 8.2 vs.12.0 months (P = .014), and mOS was 18.6 vs. 39.6 months (P = .001) for the PNI-low and PNI-high group, respectively. The ORR and DCR were significantly lower in the low-PNI group than in the high-PNI group (P = .018 and P = .017, respectively). The incidence of grade 3–4 side effects due to CDK4/6is (39.8% vs. 30.7%, P = .046) was significantly greater in the PNI-low group than in the PNI-high group. Conclusions: This study's results suggest that PNI is an easily measured and reliable indicator of prognosis in mBC patients treated with CDK4/6i and ET.