<p><i>Corchorus olitorius</i> L., Malvaceae (molokheia), is a common edible plant that is rich in terpenoids and flavonoids. For the first time, this article was planned to study the potential of <i>C. olitorius</i> root methanol extract and its nanocrystals against colon cancer (Caco-2), hepatocellular carcinoma (HepG2), and breast cancer (MCF-7) cell lines. Generally, the total methanolic extract of <i>C. olitorius</i> roots inhibited the growth of Caco-2, HepG2, and MCF-7 cells with IC₅₀ values of 18.63 ± 1.16, 37.14 ± 1.6, and 42.68 ± 1.96&#xa0;µg/ml, respectively, whereas the nanocrystals displayed significantly higher antiproliferative potential, especially against Caco-2 and HepG2 with IC₅₀ values of 12.16 ± 0.61 and 23.29 ± 1.08 µg/ml, respectively, while, MCF-7 showed IC₅₀ values of 62.50 ± 3.63 µg/ml. To discover which of the compopund/s is/are responsible for this activity, metabolomic analysis of the total methanol extract of <i>C. olitorius</i> roots was studied. It revealed the presence of a diversity of 15 metabolites largely dominated by phenolic compounds. <i>In silico</i> network analysis and molecular docking were used to explore the cytotoxic efficacy of <i>C. olitorius</i> extract against Caco-2, HepG2, and MCF-7 cancer cell lines. Central hub genes implicated in key oncogenic pathways, such as EGFR and BRAF, were pinpointed and subjected to rigorous docking protocols, using the crystal structures of EGFR (PDB ID: 1M17) and BRAF^V600E (PDB ID: 5JRQ). The docking outcomes highlight significant binding affinities for compounds within this extract, notably chloroenic acid (<b>11</b>) and rutin (<b>15</b>), implying their potential as dual inhibitors for these critical cancer pathways. These findings offer a foundational understanding for subsequent empirical studies and the potential crafting of natural novel cancer therapies.&#xa0;</p> Graphical Abstract <p></p>