Manifest V3 (The browser plugin API) severely hampers uBlock Origin's abilities to block as many things as it can.
I think the first heads-up version to the public only allowed 10,000 origins to be blocked, meaning that advertisers would only need to purchase 10,001 domains and they would be able to send ads to users again.
It's been a point of sour discussion with the chrome web team for years. They've tried to adjust it to make it more palatable with the public but advertising is just too important for Google to implement the API that users want.
Google has gone so far as to use its resources to silently take control over the web to ensure that ads remain, first with AMP based web pages, and then with FLoC advertisements. Now they've replaced that with Topics but many are eyeing that very cautiously.
It cannot do CNAME uncloaking because Chrome's extension API do not provide dns resolving like on Firefox. Another example if HTML filtering where on Firefox an extension can rewrite the HTML from requests on the fly (e.g. to remove script tags, etc.). That's also not possible on Chrome and uBlock Origin will only make use of this on Firefox. There are probably more limitations, these are just two from the top of my head.
