Liposomes and lipid nanoparticles have been actively researched and developed as drug delivery carriers owing to their many advantages, such as high biocompatibility and degradability. Their in vivo kinetics depend on the route of administration, i.e., topical or intravenous, and their physical properties, such as particle size and surface charge. Designing liposomes that regulate in vivo kinetics and ensure efficient delivery to disease sites will result in excellent therapeutic effects. However, only a handful of studies have examined whether the characteristics and constituent lipids of liposomes can control histological and in vivo kinetics. In this review, we focus on the surface charge and polyethylene glycol (PEG) modifications of liposomes and evaluate their biodistribution. On the basis of our findings, we expound the effects of the intradermal permeability, inflammatory site accumulation, and physical properties of liposomes on systemic distribution kinetics.