The present study reports on a computational model that systematically evaluates the effect of physical factors, including size, surface modification, and rigidity, on the nuclear uptake of nanoparticles (NPs). The NP-nucleus interaction is a crucial factor in biomedical applications such as drug delivery and cellular imaging. While experimental studies have provided evidence for the influence of size, shape, and surface modification on nuclear uptake, theoretical investigations on how these physical factors affect the entrance of NPs through the nuclear pore are lacking. Our results demonstrate that larger NPs require a higher amount of energy to enter the nucleus compared to smaller NPs. This highlights the importance of size as a critical factor in NP design for nuclear uptake. Additionally, surface modification of NPs can impact the nuclear uptake pathway, indicating the potential for tailored NP design for specific applications. Notably, our findings also reveal that the rigidity of NPs has a significant effect on the transport process. The interplay between physicochemical properties and nuclear pore is found to determine nuclear uptake efficiency. Taken together, our study provides new insights into the design of NPs for precise and controllable NP-nucleus interaction, with potential implications for the development of efficient and targeted drug delivery systems and imaging agents.