The use of dietary phytochemical rather than conventional therapies to treat numerous cancers is now a well-known approach in medical science. Easily available and less toxic dietary phytochemicals present in plants should be introduced in the list of phytochemical-based treatment areas. Sesamin, a natural phytochemical, may be a promising chemopreventive agent aiming to manage breast cancer. In this study, we discussed the pharmacological properties of sesamin that determine its therapeutics opportunity to be used in breast cancer treatment and other diseases. Sesamin is available in medicinal plants, especially in Sesamum indicum, and is easily metabolized by the liver. To better understand the antibreast cancer consequence of sesamin, we postulate some putative pathways related to the antibreast cancer mechanism: (1) regulation of estrogen receptor (ER-α and ER-β) activities, (2) suppressing programmed death-ligand 1 (PD-L1) overexpression, (3) growth factor receptor inhibition, and (4) some tyrosine kinase pathways. Targeting these pathways, sesamin can modulate cell proliferation, cell cycle arrest, cell growth and viability, metastasis, angiogenesis, apoptosis, and oncogene inactivation in various in vitro and animal models. Although the actual tumor intrinsic signaling mechanism targeted by sesamin in cancer treatment is still unknown, this review summarized that this phytoestrogen suppressed NF-κB, STAT, MAPK, and PIK/AKT signaling pathways and activated some tumor suppressor protein in numerous breast cancer models. Cotreatment with γ-tocotrienol, conventional drugs, and several drug carriers systems increased the anticancer potentiality of sesamin. Furthermore, sesamin exhibited promising pharmacokinetics properties with less toxicity in the bodies. Overall, the shreds of evidence highlight that sesamin can be a potent candidate to design drugs against breast cancer. So, like other phytochemicals, sesamin can be consumed for better therapeutic advantages due to having the ability to target a plethora of molecular pathways until clinically trialed standard drugs are not available in pharma markets.