Latex is a colloidal system of polymer particles suspended in water. During drying of latex, particles distribute inhomogeneously in space, compromising the final quality of the coating. To understand the mechanism of drying inhomogeneity, we integrate Optical Coherence Tomography (OCT) with gravimetric and video analysis (called “OCT-Gravimetry-Video” method) to monitor the internal structure, the water evaporation rate and the appearance of a latex coating simultaneously. Hard polystyrene particles with two different particle sizes (135 nm and 53 nm in diameter) were used as model latexes. Cracks and drying fronts were recorded by video. Packing of particles, debonding of film and shear bands were observed in reflection image and speckle variance image of OCT. Drying rate was constant and close to that of deionized water before cracking or debonding. The effects of particle size on the packing and cracking phenomena were profound and unexpected. This method provides a non-invasive and non-destructive approach to study the drying process of latex, especially with the OCT imaging on the cross-section of coating that traditional methods can hardly achieve.