Of course, a pihole will not be able to block someone who goes to the length of developing and using a custom DNS-over-TLS or DNS-over-HTTPS webpage.

Similarly uBlock origin is not available for anything else except browsers. There is nothing preventing native apps from using or pinning different nameservers. On a scale of hardness, using or pinning a specific DNS server is easy and is known to be used in wild. Custom DoT or DoH is still rare but I am aware that there will be a time when a significant chunk of internet will use it.

Name-resolution based ad-blocking is not futile yet. My pihole has alone blocked 5k+ queries in the past 24h.