It's really simple. Works only in moddable version of the game.

First, you need to install Serious Editor. In Steam, go to Library->Tools and search for a tool named "Serious Sam 2017 Editor". Install it and launch.

Once it has launched, use File->Open->Document.



Now, every game inside Fusion (HD, BFE) has its own parameters file, so you need to modify each game's file separately in order to make changes appear in all games! Let's start with BFE.
From whatever folder you're in now, navigate into "Content/SeriousSam3/Databases/" and open "GlobalGameParameters.rsc".



You should see a lot of fields with all sorts of cool stuff you can change, but today we're interested in difficulties. Scroll down a bit and you should see a field named "Game difficulties". Expand it by pressing + near it, and voila - all five difficulties are here! Open them up and you can see which parameters are customizable here and what the numbers actually are. All parameters are pretty self-explanatory.



So what can you do here? You can go and increase enemy health/damage or think speed to ridiculous levels if you feel like Serious is too easy for you.
Or you can copy all parameters from Easy/Tourist difficulty to Serious difficulty, and then Serious difficulty will be as easy as Easy/Tourist, but will have Serious enemy spawns! You can copy/paste the whole difficulty field in Editor, without changing every field one by one.

After you finish changing these parameters, do File->Save. After you press "Save" editor will throw red error message
That's because you opened a file from a game archive and saved it, but editor cannot save files back into archives, so it instead saves a copy of this file in the game directory. Check it out: in your file browser go to "Steam\steamapps\common\Serious Sam Fusion 2017\Content\" folder. You should now have "SeriousSam3\Databases" subfolder there with "GlobalGameParameters.rsc" file in it. This is the file you saved.

And as long as it stays in this folder, it will be loaded instead of the default "GlobalGameParameters.rsc" file that is in game archives whenever you launch moddable version of the game. So if you want to revert your changes, simply delete this file or move it to another place, so that it isn't replacing original file when the game loads.

That's it! If you want to change difficulty parametes of HD games (TFE,TSE), search for "GlobalGameParameters.rsc" in "Content/SeriousSamHD/Databases/" (both games use one parameters file).