Ovarian cancer remains one of the deadliest gynecological malignancies due to late-stage diagnosis and inherent resistance to conventional therapies, highlighting a critical need for novel treatment strategies. This study aimed to elucidate the apoptotic and signaling mechanisms underlying the individual and combined anticancer effects of MET and ATOR on ovarian cancer cells. The OVCAR-3 ovarian cancer cell line was exposed to varying concentrations of MET (2–256 mM) and ATOR (0.78–50 mM), alone or in combination, for 24, 48, and 72 hours. Cell viability was assessed via the MTS assay, while expression of apoptotic and signaling proteins (Bax, Bcl-2, Caspase 3, AMPK, ERK) was analyzed using Western blotting. Both MET and ATOR significantly reduced OVCAR-3 cell viability in a dose- and time-dependent manner, with calculated IC50 values of 12.77 mM (MET, p<0.0001) and 1.51 mM (ATOR, p<0.0001) at 72 hours. Combination treatment exhibited a pronounced synergistic effect, markedly enhancing apoptosis by increasing pro-apoptotic Bax (p<0.0001) and Caspase 3 (p<0.0001) and reducing anti-apoptotic Bcl-2 expression (p<0.0001). Furthermore, MET and ATOR synergistically modulated critical signaling pathways by significantly activating AMPK (p<0.0001) and suppressing ERK (p<0.0001). MET and ATOR combination demonstrated substantial synergistic anticancer efficacy in ovarian cancer cells, mediated through enhanced apoptotic signaling and modulation of AMPK/ERK pathways. These findings emphasize justification for further preclinical and clinical exploration of MET and ATOR as viable, cost-effective treatment options to improve therapeutic outcomes in ovarian cancer studies.