The song is an up-tempo, electric guitar-driven, modern rocker that features the work of E Street Band members Max Weinberg on drums, Garry Tallent on bass guitar, Clarence Clemons on saxophone, Steven Van Zandt, Clemons and Patti Scialfa on background vocals, and Nils Lofgren on a guitar part underneath Clemons's sax solo. The opening guitar riff and chord progression are somewhat reminiscent of Tommy Tutone's 1982 hit "867-5309/Jenny" with Tommy Tutone lead singer Tommy Heath quoted as saying: "Everybody’s calling me about it," and that, "I think it's close enough that if I wanted to [take legal action], I could work with it."

Springsteen's 1990s twang reasserts itself in the first verses of the down-mixed vocal line. "Radio Nowhere"'s lyrical themes address alienation and a desire for musical and social connection, a theme similar to some of his previous work:

Springsteen's lyrics appear to intentionally and repeatedly allude to his previous songs, an important artistic tradition in poetry and songwriting, continuing and reconnecting the artist's chosen themes they wish to emphasize. The lyric "I was driving through the misty rain" is likely a reference to his song "Downbound Train" on his album Born in the U.S.A. with the lyric "I feel her kiss in the misty rain." And the lyric "Dancing down a dark hole" likely refers to his song "Dancing in the Dark" from the same album.

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