Microstructure strongly affects the macroscopic properties of filter media. Many previous works studied the filter loading behavior with the single fiber or macroscale model using unresolved fiber networks, but the influence of pore-scale structure was not thoroughly investigated. In this paper, the dynamic dust loading process in structure-resolved filter media was studied with microscale simulations. The distribution of trapped particles in the filter media in depth and cake filtration regimes was recorded, and the evolution of pressure drop and filtration efficiency was analyzed in depth. This work systematically explored how structural factors such as filter thickness, solidity (i.e., packing density), bulk, and fiber orientation affect the dust holding capacity (DHC) of the filter media. We also investigated better composite filters based on various designed filters with multilayer, uniform, or gradient structures. The results showed that the filter L-bot with a finer fiber layer at the bottom had the highest dust loading capacity, 63.98% higher than the filter L-top with an inverted structure, followed by the gradient filter GI-lin and GI-exp with open pore structure near the inlet. Our work presents a strategy for designing innovative depth filter media with effective and prolonged service life. Our detailed simulation with structure-resolved fiber network and particle deposits provides a fundamental understanding of the dust loading process.