The physical environments in which microorganisms naturally reside rarely have homogeneous structure, and changes in their porous architecture can have a profound effect on microbial activities – effects that are not typically captured in conventional laboratory studies. Here, to investigate the influence of environmental structure on microbial responses to stress, we constructed structured environments with different pore properties (determined by X-ray Computed Tomography). First, using glass beads in different arrangements and inoculated with the soil yeast Saitozyma podzolica , increases in the average equivalent spherical diameters (ESD) of a structure’s porous architecture led to decreased survival of the yeast under a toxic metal challenge. This relationship was reproduced when yeasts were introduced into additively-manufactured lattice structures, comprising regular arrays with ESDs comparable to those of the bead structures. The pore ESD-dependency of metal resistance was not attributable to differences in cell density in micro-environments delimited by different pore sizes, supporting the inference that pore size specifically is the important parameter here in determining microbial survival of stress. These findings highlight the importance of the physical architecture of an organism’s immediate environment for its response to environmental perturbation, while offering new tools for investigating these interactions in the laboratory. IMPORTANCE Interactions between cells and their structured environments are poorly understood but have significant implications for organismal success in both natural and non-natural settings. This work uses a multidisciplinary approach to develop laboratory models with which the influence of a key parameter of environmental structure – pore size – on cell activities can be dissected. Using these new methods in tandem with additive manufacturing, we demonstrate that resistance of yeast soil-isolates to stress (from a common metal pollutant) is inversely related to pore size of their environment. This has important ramifications for understanding how microorganisms respond to stress in different environments. The findings also establish new pathways for resolving the effects of physical environment on microbial activity, enabling important understanding that is not readily attainable with traditional bulk-sampling and analysis approaches.