I have two setups where I have dual monitors of differing sizes. One is my personal MS Surface Go (11") which is frequently connected to my Dell 24" display as well. At work, I have a 27" 5K iMac with a 24" Cinema display (2k) as a second monitor. It works well in both cases, but there is some getting used to the arrangement, particularly since there are issues moving the mouse pointer from the larger screen to the smaller one.
You can only move between them along the area where they align. Also, when resolutions are different there can be some "jump". For example, my 11" Go's screen (1800x1200) is much higher DPI than my 24" Dell (1920x1080). Despite being only 1/2 as wide in real world inches, the Go's screen is really 90% as wide in pixels. When logically aligned (via the Windows equivalent of macOS System Preferences) so that the Dell is above the Go's internal display an aligned on their right edge, moving the mouse up from the Go's upper left corner to the Dell it cursor appears almost at the Dell's left side some 7" to the left of the physical location it had on the Go's display.
My iMac is arranged with the two monitors left and right of each other and there is a similar issue. In that case, the larger screen is also the higher DPI display. The result is a larger portion of the left edge of the iMac's screen is not covered by the smaller logical size of the Cinema display and you can't mouse over to the smaller display except through the "window" where they share a logical edge.
In short, it works well if you are good at adapting. I've been using the iMac setup for a couple of years and its foibles are second nature. I've been using the Go with the second display for 3 months or so and for me the adaption was quick and easy. YMMV