Breast cancer is the leading cause of malignancy-related death in women worldwide. Enhanced rate of relapse, high instances of distant metastasis, therapeutic resistance, and poor prognosis make it difficult to combat the alarming mortality of the disease. The currently available diagnostic paradigms of classical chemotherapy and radiation therapy, combined with surgical interventions and endocrine therapeutic approaches, often fail to counter the various clinical obstacles that are developed during the progression of the disease. The multidrug resistance (MDR), extortionate treatment expenses, and chemo-susceptible vulnerabilities encountered call for the ardent investigation of complementary and alternative medicine (CAM) for novel therapeutic shifts. CAM-based screening and the use of phytochemicals in breast cancer diagnosis are therefore embarking on elevated heights. The minimal toxicity and side effects, abundant bioavailability, and cost-effectiveness of the various natural metabolites contribute to their credit as potent antineoplastic agents. This holistic piece of updated literature primarily deals with some of the important subcategories of plant-based secondary metabolites—flavonoids, carotenoids, alkaloids, terpenoids, and polyphenols. The chapter assesses their beneficial role and mode of action in different molecular subtypes of breast cancer, with special emphasis on the more lethal subtype of triple-negative breast cancer (TNBC). The phytochemicals individually or in combination with adjuvants prevent cancer metastasis and overcome subsequent chemoresistance. The antiproliferative efficacy of these secondary compounds is generally attributed to their ability to arrest the aberrant cell cycle signaling, majorly by various cyclin modulatory mechanisms. Thus, the plant-derived candidates actively participate in repairing the cell signaling and apoptotic pathways. They control the cellular oxidative stress response mechanism, hindering angiogenesis and invasive proliferation of cancer cells. Moreover, several clinical studies also support their synergistic role in the modulation of expression of the tumor-suppressive as well as oncogenes and associated noncoding RNAs. The predicted therapeutic efficacy of phytochemicals is discussed here in the light of chemoprevention and inhibition of malignant invasion of breast cancer stem cells (CSCs) too. Preliminary studies on the different groups of phytochemicals leading to the prevention of cancer cell growth and renewal of CSC hence contribute significantly to the maintenance of optimal cellular health. In the future, with more such clinical and investigatory trials, attempts can be made to integrate such novel phytochemical-based CAM as an integral and primary line of treatment in breast cancer therapeutics. © 2023 Elsevier Inc. All rights reserved.