Liposomes have advantages as drug delivery nanomaterials including low toxicity, compatibility with a variety of therapeutics, ease of modular processing, and a diverse set of lipid building blocks to tune their physical and chemical properties. Polyethylene glycol (PEG) is a polymer widely used to create “stealth” nanoparticles (NPs). This steric coating increases the circulation time of NPs in vivo, delaying immune clearance; additionally, short peptide sequences and other moieties can be installed on the distal end of PEG to target specific tissues. When PEG-lipids are inserted into charge-neutral vesicles at very high PEG-lipid mol fraction (> 0.25), they are known to induce a structural transition to micelles. Here we examine shape changes induced by the incorporation of PEG-lipid, from low to high mol fraction, to a series of liposomes ranging from neutral to high cationic charge. Significantly, we report on how these morphological changes correlate to drug delivery efficacy of paclitaxel (PTXL)—a hydrophobic cancer drug that acts as a mitotic inhibitor, inducing apoptosis and halting the proliferation of tumor cells. Due to its hydrophobic nature, PTXL must be well solubilized for administration. In lipid bilayers and micelles, PTXL loads into the hydrophobic core (Steffes et al. Biomaterials 2017, 145, 242 https://doi.org/10.1016/j.biomaterials.2017.08.026). Here we show how liposome composition correlates to shape changes and to interactions of the particles with cells, ultimately dictating PTXL delivery. Next-generation nanomaterial delivery systems will build upon the “stealth” properties of PEGylated NPs and incorporate components such as receptor-specific peptide sequences for tumor targeting and penetration.