Cancer remains one of the leading causes of death worldwide, proving the need for more novel and selective therapies. Silver nanoparticles (AgNPs) have gained interest in cancer research due to their tunable physical and chemical characteristics and their biological reactivity. The decahedral nanoparticles (AgDeNPs) and the pentagonal nanorods (AgNRs) were synthesized photochemically and thermochemically, respectively, with varying sizes and shapes. The current study investigates the effect of the nanoparticles’ size and shape on cytotoxic and apoptotic responses in colon carcinoma cells. The particles’ distinct morphologies were confirmed through UV-Vis spectroscopy, dynamic light scattering, and transmission electron microscopy, revealing monodispersed AgDeNPs of 41 nm and 89 nm and AgNRs of 90 nm and 120 nm. Cytotoxicity assessment via MTT assays showed a concentration-dependent decrease in cell viability, with AgNRs displaying higher toxicity than that of AgDeNPs. The half-maximal inhibitory concentrations (IC₅₀) were 177.2 µM (41 nm decahedra), 254.1 µM (86 nm decahedra), 46.0 µM (90 nm rod), and 175.6 µM (120 nm rod). Western blot analysis of cell lysates treated with the IC₅₀ concentrations indicated that AgNRs induced an increase in the expression of p53 and Bax/Bcl-2 ratios, while pAkt/Akt levels decreased, suggesting mitochondrial apoptotic pathway activation. AgDeNPs did not significantly affect the expression of pAkt or Bcl-2, which is consistent with pro-survival signaling. Collectively, these findings demonstrate that nanoparticles’ geometry and size modulate cellular behaviour, with AgNRs promoting apoptosis and AgDeNPs favouring cell survival, thus establishing a structure-to-function relationship. To guide cellular outcomes, this study suggests that the tunable nanoparticle size and morphology offer insights into targeted delivery to tumor tissue.