The sixth Madame Hydra first appeared during the Nick Fury vs. S.H.I.E.L.D. limited series, in which she is dispatched by the Supreme Hydra to kill Nick Fury and recover his body. Unknown to her, the Supreme Hydra is actually a Deltite, an advanced Life Model Decoy that desires to prolong its own existence by extracting the secrets of the Infinity Formula from Fury's body. Madame Hydra fails, and ends up forming a temporary alliance with Fury in order to thwart the Deltite, who has gained control of S.H.I.E.L.D., Hydra, and Roxxon Oil.

It is revealed that she is the sixth woman to ascend to the title of Madame Hydra, the first having been Viper. She is also shown to be an accomplished swordswoman. She becomes linked to Alexander Pierce, who she nearly kills during a confrontation with Nick Fury.

Madame Hydra is captured and placed in an institution until she is freed by agents of the Yellow Claw. Through him, she manages to regain her position within Hydra. However, this is short-lived, and she apparently dies when her skysled explodes. Madame Hydra VI has yet to reappear.