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Yes, you can install life-saving mods that make Binding of Isaac much easier and still unlock stuff, you’ll just need to install mods manually.
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Steam User Sorario Prosperity had the same problem, and figured out a way to circumvent the annoying limitations that are built into Steam. All your progress won’t mean anything, basically, and new characters can’t be earned.
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There’s a big drawback to using mods though - enabling a mod will turn-off achievements and unlocks in-game. Instead of slogging through the main game and hoping the RNG rewards you with great loot, many players opt to use Steam Workshop mods to make things easier. The Binding of Isaac: Rebirth just received another DLC upgrade that, surprise-surprise, makes a difficult game even harder.
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