Gold nanoparticles (AuNPs) with different geometry have been demonstrated to provide significant advantages in enhancing cellular uptake and improving the efficacy of photothermal therapy (PTT). In this study, we synthesized spherical (AuNSs), cube-shaped (AuNCs), and rod-shaped (AuNRs) using the seed-mediated growth method in which cetyltrimethylammonium bromide (CTAB) was used as stabilizing agent. To investigate the impact of nanoparticle geometry on their potential for PTT and their ability to interact with and penetrate cell membranes, we employed two different model membranes, 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) and endothelial model membrane (EMM). The biophysical interaction between the AuNPs having different geometry and model membranes was investigated using 2D model. Similarly, we evaluated the efficiency of cellular uptake for these AuNPs and found that AuNRs exhibited greater cellular uptake than the other shapes, despite the initially higher interaction of AuNCs with the DPPC monolayer due to stronger electrostatic interactions. Furthermore, when utilizing a more realistic model membrane (EMM), we observed highly successful biophysical interactions of AuNRs regarding cellular uptake extent. Collectively, our findings suggest that the surface charge and geometry of AuNPs play a crucial role in determining their photothermal therapy potential and cellular uptake efficiency. Moreover, AuNRs are promising candidates for PTT and drug delivery applications.