Background: The emergence of molecular targeted therapies (MTTs) has altered the treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (MBC). The objective of this study was to describe treatment patterns, clinical outcomes, and safety profiles for patients with HR+/HER2− MBC treated with palbociclib, abemaciclib, or everolimus in clinical practice. Methods: Forty-five patients with HR+/HER2− MBC were enrolled; 40 received MTT as the third line or later and 5 received MTT as the first/second line. The results were compared with those of clinical trials. Results: Median overall progression-free survival (PFS) was 5.3 months (95% confidence interval CI 2.8-8.4), and PFS was similar for patients receiving first/second line (5.5 months, 95% CI 1.8-) and third line or later (5.1 months, 95% CI 2.8-9.4) treatments. Eleven patients continued with the same regimen for >1 year; treatment is ongoing for 15 patients. In 23 patients (51%), everolimus was administered before cyclin-dependent kinase (CDK) 4/6 inhibitors. The most frequent grade 3 or worse adverse event (AE) with CDK4/6 inhibitors was neutropenia, whereas grade 3 or worse AEs with everolimus were Pneumocystis pneumonia, sepsis, and stomatitis. Conclusions: MTT was mostly used in third or later lines, and PFS was similar for patients receiving first/second line and third or later line treatments. However, this study included heavily treated patients and a small number of cases. Treatment options should consider maximal patient benefit, as indicated by the results of clinical trials.