Surviving 5 or 6 kings, Hetepheres II must have been one of the longest living members of the royal family of the 4th Dynasty.
She was a daughter of Kheops, probably born during the reign of her grandfather, Snofru or during the early years of her father's reign. A fragmentary titulary found in the tomb of Meretites, could indicate that Meretites may perhaps have been the mother of Hetepheres II.
At the latest during the reign of Kheops, she married her brother Kawab, with whom she had several children: the princes Duaenre, Kaemsekhem and Mindjedef and the princess Meresankh III, who would later marry Khefren.
After the death of her first husband, she married another of her brothers, Djedefre. When Djedefre succeeded to the throne, after Kheops' death, Hetepheres II became a queen. It is not know whether she had any children with Djedefre.
She was widowed again when Djedefre died. She then probably married Ankhaf, although it is also possible that Ankhaf's wife was another member of the royal family of the 4th Dynasty.
The marriage of her daughter, Meresankh III, to her late second husband's successor Khefren made Hetepheres II the mother-in-law of the new king. A mark of her affection for Meresankh may perhaps be seen in the fact that Hetepheres II had her own mastaba in the eastern cemetery of Giza converted into a tomb for her daughter.
She finally died early in the reign of Shepseskaf, the son and successor of Mykerinos and had thus witnessed the reigns of 5 (perhaps 6, if she was born during the reign of Snofru) kings of the 4th Dynasty.