The evolution of microstructure in drying coatings is essential to the final film properties. Understanding this process and the microstructure during drying is a common question in the coatings industry. There is often a separation between the predicted film and the final applied film due to evolving rheology and particle-scale interactions. There are few techniques that are able to provide this information in situ. This work focuses on tracking fluorescent silica particles that behave as surrogate pigment using high-speed laser scanning confocal microscopy to give the time evolution of microstructure as a function of the formulation. Specifically, the addition of cellulose-based rheology modifiers is examined to understand the impact of rheology modifiers on the drying process and resulting microstructure. Clear changes in particle stability, such as the onset of depletion or other attractive interactions, are observed during drying that significantly alter the microstructure evolution during drying. Using the 3D particle locations, the evolution of this microstructure allows thorough statistical analysis, resulting in simulation-like detail from physical experiments.