Traditional star formation subgrid models implemented in cosmological galaxy formation simulations, such as that of V. Springel & L. Hernquist (hereafter SH03), employ adjustable parameters to satisfy constraints measured in the local Universe. In recent years, however, theory and spatially resolved simulations of the turbulent, multiphase, star-forming interstellar medium (ISM) have begun to produce new first-principles models, which when fully developed can replace traditional subgrid prescriptions. This approach has advantages of being physically motivated and predictive rather than empirically tuned, and allowing for varying environmental conditions rather than being tied to local-Universe conditions. As a prototype of this new approach, by combining calibrations from the TIGRESS numerical framework with the pressure-regulated feedback-modulated (PRFM) theory, simple formulae can be obtained for both the gas depletion time and an effective equation of state. Considering galaxies in TNG50, we compare the “native” simulation outputs with postprocessed predictions from PRFM. At TNG50 resolution, the total midplane pressure is nearly equal to the total ISM weight, indicating that galaxies in TNG50 are close to satisfying vertical equilibrium. The measured gas scale height is also close to theoretical equilibrium predictions. The slopes of the effective equations of states are similar, but with effective velocity dispersion normalization from SH03 slightly larger than that from current TIGRESS simulations. Because of this and the decrease in PRFM feedback yield at high pressure, the PRFM model predicts shorter gas depletion times than the SH03 model at high densities and redshift. Our results represent a first step toward implementing new, numerically calibrated subgrid algorithms in cosmological galaxy formation simulations.