Solid-phase stress is a major factor shaping the complex behaviors of particle–fluid systems. However, uncertainties and inconsistencies can be found among the various models proposed. This work pays attention to the effect of mesoscale structures, that is, the heterogeneity of particle distribution at a scale of statistical meaning but no significant flow field variation, on the solid-phase normal stress, or pressure. Using a bottom-up statistical method, the solid-phase pressure in liquid- and gas–solid flows is investigated by particle-resolved direct numerical simulation (PR-DNS). It is found that, in almost uniform liquid–solid flows, the solid-phase pressure is not well predicted by classical kinetic theory of granular flow (KTGF) due to the presence of interphase force, although KTGF applies much better to single-phase granular flows. In gas–solid flows, with increasing heterogeneity described by structural functions, the statistical solid-phase pressure becomes significantly larger than that in corresponding homogeneous flows. It reveals that mesoscale structures strongly affect solid-phase pressure, and suggests the deviation from classical KTGF in heterogeneous gas–solid flows can be attributed to both the interphase forces (mainly drag) and mesoscale structures. The coefficients in the solid-phase pressure models in KTFG are modified, fitting the statistical results of both homogeneous and heterogeneous particle–fluid flows.