This paper explores the influence of pH and ionic strength of polyelectrolyte solutions as a simple and chemically amenable strategy for tuning the structure and drug delivery properties of polyelectrolyte multilayers produced via layer-by-layer technique. Carboxymethylcellulose/chitosan films were buildup under different pH (4.0 and 6.0) and salt concentrations (0 or 0.2 M NaCl) conditions. Systematic data analyses using Design of Experiments indicate that high ionic strength favors the formation of thinner and rougher films. Higher pH led to the formation of thinner and rougher films, attributed to the substantial decrease in the degree of ionization of carboxymethylcellulose and the random coil conformation of chitosan at the outermost layer, respectively. The random coiled conformation of chitosan near to neutral pH also seems to be the major factor to increase the surface film roughness under wet conditions. Drug delivery tests performed with Rose Bengal (model drug) indicate a predominant non-Fickian release mechanism for most of the buildup conditions tested. Densely packed multilayered films obtained at pH 6.0 and 0.2 M NaCl resulted in a faster, Fickian release mechanism, with minimal changes in surface morphology under wet conditions. The total amount of drug released shows a significative influence of only the polyelectrolyte solution pH, associated with the higher amount of free amino groups of chitosan at the film surface at higher pH conditions. These findings shed light on a strategy to develop functional coatings with tailored structural and drug delivery properties by simply controlling film depositions conditions.