Ocean survey vessel HMS Scott is earmarked to sail into the city’s harbour on Saturday afternoon.
The 13,500-tonne is the only one of its kind and one of the largest vessels in the fleet.
It will be the first visit to Portsmouth made by the 430ft vessel in about a decade.
The huge survey ship had previously called the city home between August 2008 and June 2009, when she underwent a major overhaul at the naval base.
Her latest arrival is scheduled to take place at about 1pm.
It follows a recent successful deployment to the south Atlantic for Scott and her crew.
The ship sailed back to her base in Devonport, Plymouth, at the end of March, having spent nearly 10 months at sea.
The hi-tech vessel is used to scour the world’s oceans, gathering data which assists both military operations and can also update seafaring charts produced for mariners worldwide.
Her latest stint at sea saw her 48-strong crew sailing through the Atlantic and visiting the Caribbean.
Commissioned in June 1997, the survey vessel is packed with a sophisticated array of sensors to help map up the ocean floor.
Scott used its equipment in the wake of the deadly Boxing Day tsunami of 2004, which killed about 228,000 people, to help scientists understand how the tragedy unfolded.