In this study, we systematically evaluate sample preparation strategies, data acquisition modes and data-analysis approaches for both labeled and label-free proteomics, with the explicit goal of maximizing throughput and quantitative depth using Orbitrap-based instruments operating below 50Hz scan rates and without reliance on automation. Here we benchmarked DIA and TMT based acquistion of pSILAC data (2-SILAC and 3-SILAC)on Orbitrap Ascend, Lumos and Q-Exactive HF