After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.