<p>Phytochemicals are of paramount importance in combating various diseases such as cancer, diabetes, and coronary diseases. These bioactive compounds of plant origin are gaining importance in cancer therapy due to the inevitable negative effects of modern medicine. <i>Ficus rumphii</i> is an under-explored species of the family Moraceae which has been identified as a potential therapeutic for various ailments in traditional medicine. The study identifies the phytocompounds from the methanol extract of these plant leaves (Fr-ME) by GC–MS and its antioxidant, antimicrobial, antiproliferative and cytotoxicity potential were studied in vitro. Additionally, a network pharmacology approach was adopted for the target prediction of the phytochemicals for the suppression of renal cancer. These targets were studied in silico by molecular docking and dynamics. Since the inactivation of P⁵³ through MDM2-P⁵³ interaction is one of the major causes of apoptosis inhibition and associated renal carcinoma, the suppression of MDM2 activity through <i>F. rumphii</i>-derived Lanosterol and β-amyron can prevent the carcinogenic progression by the induction of cell cycle arrest and apoptotic pathway. This study is the first-ever report for the comprehensive analysis of the therapeutic properties of <i>F. rumphii,</i> especially for its anticancer potential and is established by in vitro and in silico studies.</p> Graphical Abstract <p></p>