Someone who makes small adjustments or improvements to something, or slang for someone addicted to methamphetamine.
From 'tweak' (possibly from 'twitch') plus '-er' (agent suffix). The standard sense emerged in the 1990s in tech culture; the slang drug sense came later.
This word shows how tech culture invents vocabulary: tweakers are the people who obsess over tiny improvements—the same mentality that built the internet! But the slang sense shows how the same words get totally different meanings in different communities.
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