Angela Berecz, 53, was found dead on the houseboat where she lived with her partner in October 2020.
She suffered from significant health issues and was found unresponsive in a recliner chair.
A pathology review indicated her death was not suspicious and was related to her medical conditions.
But Detective Superintendent Des Bray said fresh information received recently had cast a new light on the woman's death.
He said police now have a new and suspicious cause of death, a suspect and a motive, but declined to elaborate further for operational reasons.
"This new development has come as a shock for Angela's family, but they are assisting with the investigation," he said.
"She was a vulnerable member of our society and detectives are doing everything they can to ensure that anyone responsible for Angela's untimely death is brought to justice."
Supt Bray said Ms Berecz and her partner had lived on a houseboat, moored on the Murray River at Blanchetown, for about six years.
He said given the circumstances it was most likely the person or persons responsible for her death were known to her.
"She lives on a houseboat, she's mostly immobile .... so it's more likely than not it's somebody known to her," Supt Bray said.
"The investigation is in its infancy but we're very fortunate we do have a suspect and we're exploring the possibility of more than one person being involved.
"This is not a job where we don't have any leads. This is a job where we have a clear focus."
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