Graphics card length and thickness. The card is the biggest object in the build and it decides which case is possible. Tom's Hardware notes that most Mini-ITX cases released in the last few years accept full-length two- or three-slot cards, but the smallest still don't, and thickness matters as much as length because a thick card can block the side panel or the power connector. I check the card against the case's published clearances before I order either one.
Cooler height. Many ITX cases cap the processor cooler at a height that rules out the big tower air coolers I'd use in an ATX build. That leaves low-profile air or a compact liquid cooler, each with its own clearance fight against the memory and the graphics card. My air vs. liquid cooling page covers the tradeoff; in a small box it's usually decided by what fits.
SFX power supplies. A standard ATX supply is too big for most true ITX cases, so the build uses the SFX form factor. Corsair's published spec for its SF-series SFX units lists a 100mm by 63mm by 125mm footprint, well under the depth of a standard unit. SFX supplies cost more per watt, have shorter cables and a smaller fan that works harder. A good one is quiet; a cheap one is not.
Airflow. Fewer fan mounts, tighter panels, parts stacked closer together. A tower can be sloppy about airflow and get away with it. A small case can't.
Fewer drive bays and slots. One expansion slot, two memory slots, and room for a drive or two beyond the NVMe slots. A large 3.5-inch drive collection belongs in a different build.
Harder to upgrade later. The next graphics card has to fit the same envelope, the supply has to carry it, and the memory ceiling is whatever two slots hold. I plan for that, but the box will never be as flexible as a tower.
Heat is the whole problem. A processor and graphics card make the same heat in any case. AMD's own spec sheet for its top desktop Ryzen lists a 170W default TDP and a 95°C maximum operating temperature, and the chip will slow itself down at that ceiling rather than fail. In a tower you rarely get there. In a small case, without deliberate cooling choices, you get there quickly, and the PC you paid for quietly runs slower than it should.