1) Pick a build tool (gulp, grunt, webpack - if you don't want an option, use webpack). You don't need a build tool but it helps with transpilation and it's a good base for the future.
2) Make or copy/adapt your build tool's config file to use Babel so you can use the latest ES version but compile down to work in browsers. You'll have to Google but these exist all over the place and they aren't confusing.
3) Pick a front end framework. Do you like Vue? It doesn't really matter because they're all doing basically the same thing in slightly different ways (like Rails, Django, Sinatra, Flask, etc).
You're good to go. It's not more difficult than setting up a Python, C, or any other environment, you simply have options. Hell, if you're doing terminal apps, you gotta decide between ncurses, blessed, termbox, raw escape sequences and so on. The JS world really isn't different than anything else.