Strategies for cell-specific targeting and delivery of single-wall carbon nanotubes (SWCNTs) have made significant advancements over recent years. However, control of sub-cellular localization, an important criterion for many biomedical applications, remains largely unexplored. I will present our experimental work demonstrating how different molecules that are used to non-covalently suspend hydrophobic SWCNTs in aqueous conditions also influence cellular processing and localization. We utilized complementary imaging modalities including real-space fluorescence imaging, confocal Raman imaging, and fluorescence lifetime imaging microscopy to show that SWCNTs dispersed using the membrane active tri-block copolymer Pluronic^® F-127 (PF127) were endocytosed into cells by the millions but eventually escaped endosomes and altered F-actin structures. In contrast, SWCNTs dispersed with the protein bovine serum albumin (BSA) were endocytosed into cells at similarly high levels but remained in the endosomal pathway, ultimately co-registering with endoplasmic reticulum and vesicles. Interestingly, cellular exposure to SWCNTs–BSA in the presence of the endosome disrupter, chloroquine, led to altered F-actin structures that were similar to the alterations induced by cellular exposure to SWCNTs–PF127. These results suggest that PF127 facilitated endosome escape and that SWCNTs might have an energetically favorable interaction with stiff, filamentous structures inside the cell. Thus, our results provide a design principle for non-covalent surface modifications of SWCNTs that do not degrade the desirable, intrinsic SWCNT properties but provide differential trafficking to intracellular compartments for sub-cellular biomedical applications.