This review article explores the cellular uptake and intracellular trafficking of nanoparticles (NPs), which are increasingly used in nanomedicine for disease treatment and diagnosis. The study highlights the different pathways by which NPs enter cells, such as phagocytosis, pinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin- and caveolae-independent endocytosis. It also discusses how the physicochemical properties of NPs, including size, shape, surface charge, and surface chemistry, influence their cellular uptake and intracellular trafficking. The review emphasizes the importance of understanding these mechanisms to design safe and effective NPs for biomedical applications, such as drug delivery and imaging. Additionally, it covers the role of NP elasticity and surface modification in cellular interactions and intracellular trafficking. The article concludes by underscoring the need for further research to address the potential hazards of NPs in consumer products and their impact on human health.This review article explores the cellular uptake and intracellular trafficking of nanoparticles (NPs), which are increasingly used in nanomedicine for disease treatment and diagnosis. The study highlights the different pathways by which NPs enter cells, such as phagocytosis, pinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin- and caveolae-independent endocytosis. It also discusses how the physicochemical properties of NPs, including size, shape, surface charge, and surface chemistry, influence their cellular uptake and intracellular trafficking. The review emphasizes the importance of understanding these mechanisms to design safe and effective NPs for biomedical applications, such as drug delivery and imaging. Additionally, it covers the role of NP elasticity and surface modification in cellular interactions and intracellular trafficking. The article concludes by underscoring the need for further research to address the potential hazards of NPs in consumer products and their impact on human health.