The MOBILion MOBIE system is a relatively new platform offering high ion mobility spectrometry (IMS) resolving power and resolution. While these advancements present encouraging opportunities for isomer separations and improved molecular annotation, previous studies have noted that collision cross section (CCS) values collected on the MOBIE and other traveling wave (TW) systems possess bias in calculated CCS values that limits the functionality of translating CCS libraries across multiple IMS platforms. Though these challenges persist, MOBILion recently released a software update (EyeOn v.2.3) that provides the capability of utilizing variable traveling wave profiles, which modulate the applied TW amplitude and frequency over the duration of each IMS scan to provide optimal transmission, IMS resolution, and scan speed. In this work, 5 variable TW profiles are assessed alongside a legacy "static" method for application toward future small-molecule workflows, tested herein with 3 model systems: per- and polyfluoroalkyl substances (PFAS), bile acids, and oxylipins. Using 3 primary evaluation metrics, including (1) ion transmission, (2) IMS resolution of isomeric species, and (3) relative ease of CCS conversion and mobility filtering, the collective results illustrate that the "Full" TW profile possesses many advantages when analyzing small molecules for nontargeted applications. Although the bias in TW-based CCS measurements vs previous DTIMS values remains, utilizing CCS values obtained with a consistent variable TW profile enables a linear calibration procedure, which facilitates routine mobility filtering of IMS-MS data by CCS and represents a needed improvement for streamlining both data acquisition and subsequent analysis.