We present a first-principles-based multiscale simulation framework for quantitative predictions of the high-energy part of the ultraviolet photoelectron spectroscopy (UPS) spectra of amorphous molecular solids. The approach combines a deposition simulation, many-body Green's function theory, polarizable film embedding, and multimode electron-vibrational coupling and provides a molecular-level view on the interactions and processes giving rise to spectral features. This insight helps bridging the current gap between experimental UPS and theoretical models as accurate analyses are hampered by the energetic disorder, surface sensitivity of the measurement, and the complexity of excitation processes. In particular, this is relevant for the unambiguous determination the highest occupied molecular orbital energy (HOMO) of organic semiconductors, a key quantity for tailoring and engineering new optoelectronic devices. We demonstrate the capabilities of the simulation approach studying the spectrum of two isomers of 2-methyl-9,10-bis(naphthalen-2-yl)anthracene as archetypical materials showing a clearly separated HOMO peak in experiment. The agreement with experiment is excellent, suggesting that our approach provides a route for determining the HOMO energy with an accuracy better than 0.1 eV.