The story takes place at the court of King Herod in Tiberias where John the Baptist (Jochanaan) is held prisoner in a cistern. The voice of the prophet attracts Salome, the beautiful stepdaughter of the king desired by many at court, primarily by her stepfather, who has a morbid passion for her. The princess, feeling irremediably attracted to Jochanaan, tries in vain to seduce him and after yet another refusal she decides to ask for his head as a pledge from Herod, who accepts only after Salome's performance in a very sensual dance of the seven veils. The girl's wish is thus fulfilled but the horror reaches its peak when Salome, in a necrophilic impulse, kisses the mouth of the beheaded prophet, an act for which she will be executed. Wilde's drama had attracted Strauss not only for the audacity of the theme covered, but above all for the presence of characters so tormented and neurotic that it would have allowed him to create extreme music, capable of following the violent disturbances of Salome's mind and the turbid thoughts of Herod and his courtiers.

The disorder of the psyche finds a perfect counterpart in a musical score where the mammoth orchestra is involved in a tumultuous vortex of dissonances and where an agitated, hysterical vocality prevails, far from any lyrical impulse.