We have described the influence of selected factors that increase the toxicity of nanoplastics (NPs) and microplastics (MPs) with regard to cell viability, various types of cell death, reactive oxygen species (ROS) induction, and genotoxicity. These factors include plastic particle size (NPs/MPs), zeta potential, exposure time, concentration, functionalization, and the influence of environmental factors and cell type. Studies have unequivocally shown that smaller plastic particles are more cytotoxic, penetrate cells more easily, increase ROS formation, and induce oxidative damage to proteins, lipids, and DNA. The toxic effects also increase with concentration and incubation time. NPs with positive zeta potential are also more toxic than those with a negative zeta potential because the cells are negatively charged, inducing stronger interactions. The deleterious effects of NPs and MPs are increased by functionalization with anionic or carboxyl groups, due to greater interaction with cell membrane components. Cationic NPs/MPs are particularly toxic due to their greater cellular uptake and/or their effects on cells and lysosomal membranes. The effects of polystyrene (PS) vary from one cell type to another, and normal cells are more sensitive to NPs than cancerous ones. The toxicity of NPs/MPs can be enhanced by environmental factors, including UV radiation, as they cause the particles to shrink and change their shape, which is a particularly important consideration when working with environmentally-changed NPs/MPs. In summary, the cytotoxicity, oxidative properties, and genotoxicity of plastic particles depends on their concentration, duration of action, and cell type. Also, NPs/MPs with a smaller diameter and positive zeta potential, and those exposed to UV and functionalized with amino groups, demonstrate higher toxicity than larger, non-functionalized and environmentally-unchanged particles with a negative zeta potential.