The small PCB of a Mini-ITX motherboard means there are some inevitable compromises compared to an ATX motherboard. The two biggest ones are the lack of more than one PCIe expansion slot, and less space for multiple M.2 slots.
With a Mini-ITX system, you won't have a problem installing a single graphics card and a small number of SSDs or HDDs, but if you want more than two NVMe SSDs, you will have to go for something larger. Budget ATX boards will typically have at least three, while more expensive boards can have up to five. A high number of SATA ports is becoming rare on any motherboard, but it's still possible to find boards with up to eight. Such a high number is impossible on a Mini-ITX motherboard.
Mini-ITX motherboards come with only two memory slots. It's less of a concern these days as higher capacity memory is available, but if 96GB to 128GB of memory is not enough for your demands, you'll have to go with a four DIMM slot board, which will give you the ability to install up to 256GB.
Some of the cheaper Mini-ITX motherboards might not have high spec VRM designs or large heatsinks. Even the cheapest boards will work well enough, but if you plan to go with a powerful multi-core CPU, and you plan to thrash it, it's advisable to spend a little more on a higher spec Mini-ITX board, or go with an ATX option.