As others already pointed out, KSP is the one that rules them all. Totally recommended. Also, not a game rather than an educational application, but Universe Sandbox may interest you, especially if you're even slightly interested in astronomy. ;)

When it first came out on GOG wasn't it using an older build than steam? I do believe that's been rectified, but I thought that's where a lot of those complaints originated from.

GOG ALWAYS has an older build than Steam.

I love GOG and prefer it over Steam any day of the week, but this ain't the best place in the world for reliable and current updates. ;P

OP didn't limit his scope to only games on GOG, though...which is good, as there really aren't very many "science-y" games here, even if one counts the handful of programming-related ones.

I'm surprised nobody mentioned RobotWar or Crobots.

I'll also suggest something a bit more tenuous: Virtual Pool 3. I bought it back when it came out because the box had a guarantee that it would improve my real life pool game or my money back and it actually did. The physics in it are spot on and the video clips of Jeanette Lee are informative.

Unfortunately, I doubt my beloved Island of Dr. Brain by Sierra On-Line is available on GOG. That, along with the other games in its series, has a lot of math and science puzzles that require you to think (and study the documentation). I appreciate them more as an adult, because some of those puzzles were simply too unfathomable when I was a youngster. I still have the CD, some floppies, and the EncycloAlmanacTionaryOgraphy booklet.

I picked up, human resource machine, last night. So far it is very satisfying to play. It just might be the most satisfaction that I have ever felt from playing a game. Maybe I will try TIS-100 next, but I'm enjoying this one for now. Thanks for the recommendation.

I would like to find other games in other areas of math, science, and technology that are equally well put together and as satisfying to play. Hopefully some of the other recommendations in the theread will live up to this one.

Gizmos and Gadgets is very science-oriented, but the puzzles are much more on the level of "kids with little knowledge of the basics", not "adults looking for a challenge".

Since you seemed receptive to TIS-100, I'm going to go ahead and suggest looking into the other Zachtronics games. There's one strategy one I don't really know anything about, but the other four (including TIS-100) are all puzzlers, requiring some amount of logic to solve.

I've heard multiple people describe the games as being good at making you feel stupid... Especialy in reguards to Shezhen I/O and Opus Magnum.
Their latest work, Opus Magnum, isn't on GOG, but I've heard good things about it as well if you don't mind stepping over to steam to get it.

They aren't all strictly math/science type games, but they are puzzlers that need that need similar types of problem solving brain workouts.

Can you go into more detail about this? I'm very interested in astronomy (admittedly more the stargazing aspect than the actual physics of it all, but still), and while I've seen Universe Sandbox around, like most other games with sandbox/simulator in the title, I avoided it.

Speaking of Zachtronics, their newest game Opus Magnum looks really cool, which is based on one of their old flash games. Those programming games look too much like work to me, but this one looks quite fun to just tinker with. I'm hoping it'll come to GOG as well on release; seeing as all of their other games are present I figure there's a very good chance of that happening.

Yeah, I mentioned that one further down in my post. I do hope they bring it here. It looks like something I will buy eventually, and I'd rather buy it here.

And I guess that's why it looks so much like that old flash game. Didn't realize it was the same people.
If anyone still has flash installed and is interested you can check out the old flash game here: http://www.zachtronics.com/the-codex-of-alchemical-engineering/

That's what happens when I skim just the first half of the post. =/

Did anyone mention Spacechem?