Fluorocarbon nanodroplets, similar to 100 to similar to 400 nm in diameter, are of immense interest in a variety of medical applications including the imaging and therapy of cancer and inflammatory diseases. However, fluorocarbon molecules are both hydrophobic and lipophobic; therefore, it is challenging to synthesize fluorocarbon nanodroplets with the optimal stability and surface properties without the use of highly specialized surfactants. Here, we hypothesize that we can decouple the control of fluorocarbon nanodroplet size and stability from its surface properties. We use a simple, two-step procedure where standard, easily available anionic fluorosurfactants are used to first stabilize the fluorocarbon nanodroplets, followed by electrostatically attaching functionalized polyelectrolytes to the nanodroplet surfaces to independently control their surface properties. Herein, we demonstrate that PEGylated polyelectrolyte coatings can effectively alter the fluorocarbon nanodroplet surface properties to reduce coalescence and its uptake into phagocytic cells in comparison with non-PEGylated polyelectrolyte coatings and uncoated nanodroplets, as measured by flow cytometry and fluorescence microscopy. In this study, perfluorooctyl bromide (PFOB) was used as a representative fluorocarbon material, and PEGylated PFOB nanodroplets with diameters between 250 and 290 nm, depending on the poly(ethylene glycol) block length, were prepared. The PEGylated PFOB nanodroplets had superior size stability in comparison with uncoated and non-PEGylated polyelectrolyte nanodroplets in saline and within macrophage cells. Of significance, non-PEGylated nanodroplets were rapidly internalized by macrophage cells, whereas PEGylated nanodroplets were predominantly colocalized on the cell membrane. This suggests that the PEGylated-polyelectrolyte coating on the charged PFOB nanodroplets may afford adjustable shielding from cells of the reticuloendothelial system. This report shows that using the same fluorosurfactant as a base layer, modularly assembled PFOB nanodroplets tailored for a variety of end applications can be created by selecting different polyelectrolyte coatings depending on their unique requirements for stability and interaction with phagocytic cells.