Do I ever need explicit allowSyntheticDefaultImports if esModuleInterop is true configuring TypeScript transpilation?

If you mean can you leave allowSyntheticDefaultImports undefined and define only esModuleInterop, the answer should be YES moving forward, but there has been an issue with this. PR #26866 seems to be a fix, only merged September 17, so it there may be some risk in the short term.

As why both exist, I believe these were both a part of addressing compatibility issues with imports of Babel-transpiled modules, the original PR added the allowSyntheticDefaultImports option to certain compile-time messages, but in practice didn't address the runtime behavior of the imports. So --esModuleInterop was added later. See TypeScript-Handbook/#816 for discussion of how to update the docs...

Well, my understanding is that the allowSyntheticDefaultImports is for being able to load CommonJS libraries in a simpler way if you target es6+ (in dev time) while esModuleInterop is for simplifying these imports (in runtime) if you target for example AMD (like I do).

According to the docs you shouldn't need to specify allowSyntheticDefaultImports explicitly if you have esModuleInterop enabled, but the reason I had to enable also the allowSyntheticDefaultImports is that Resharper seems to look at that that flag when doing syntax checking in Visual Studio. Sure it built and worked ok anyway with only esModuleInterop, but I got a lot of red warnings from Resharper until I enabled also the other flag.

According to the relevant documentation here : https://webpack.js.org/guides/typescript/, both options have different significance. Based on the project code and dependent library syntax, either/both options may be required.