One step up from kill it with fire, usually followed by the phrase "it's the only way to be sure."
A paraphrasal of Ripley's line in the 1986 film 'Aliens': "I say we take off and nuke the entire site from orbit. It's the only way to be sure."
Generally used in response to a clusterfuck, or anything largely weird or gross that needs killing or otherwise dealing with.
Mike: Guys, termites have invaded my house, what should I do?
Dave: Nuke it from orbit!
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