The main differences between the Logitech MX Keys S Combo and the Logitech MX Keys Combo for Business Gen 2 are as follows:

- The MX Keys S Combo is a newer version with slightly different keycaps that are a bit firmer and more tactile, which affects the typing feel. The older Business Gen 2 has a slightly softer typing feel.
- The MX Keys S offers automatic brightness adjustment of the backlight and more customisation options via the software, while the Business Gen 2 only allows on/off for the backlight.
- Both support Bluetooth and the Logi Bolt receiver, with the Business Gen 2 being advertised specifically for business environments with encrypted Bolt dongle and Management functions.
- The Business Gen 2 is described as particularly quiet and stable with a metal plate, including an ergonomic palm rest that provides all-day comfort.
- The product names and marketing differ: the Business Gen 2 is labelled "MX KEYS FOR BUSINESS" and focuses on business features, while the MX Keys S Combo is more of an upgrade to the normal MX Keys series.

Overall, the differences are rather subtle and mainly concern typing feel, lighting control and business-specific functions. The hardware and design are very similar.