This picture is based on the biblical story of Samson and Delilah. It is painted to look like a cameo - a miniature relief in the different strata of a precious stone. Such carvings by Roman gem-cutters were admired and collected in Mantegna's circle.
In the biblical story (Judges: 16), Delilah reveals the secret of Samson's strength (his uncut hair) to his enemies, and he is captured. This was sometimes seen as an example of a woman's treachery: Delilah betrayed her lover for money.
The painting is a companion with one of 'Judith and Holofernes'. They form a contrast since Judith serves her nation by killing its greatest enemy, whereas Delilah destroys the nation's greatest hero. These may, however, have been part of a series of paintings of famous women.