The biggest difference, in my opinion, is that Plasmo is a framework, which means you have to learn its abstractions and rely on specific samples tailored for these abstractions to create new extensions. There are config files and specific rules to follow that are not necessarily related to browser extensions.
On the other hand, Extension.js allows developers to create extensions using the standard extension APIs and abstracts only the configuration files, without the need to learn the tooling specifics. This way, a sample from Chrome or MDN that works with a manifest file as the source of truth requires no refactoring to work with Extension.js, making it easier to get started and prototype new projects.
https://www.plasmo.com/