Scottish Water's work will involve contractors carrying out detailed surveys of ground conditions at various locations.
It is the biggest project in the Greater Glasgow area's waste water network in more than a century.
The aim is to improve river water quality in the Clyde and its tributaries, enable the area to grow and develop, tackle sewer flooding and deal with the effects of increased rainfall and climate change.
The site investigation work will include the use of a rig on a barge which will take samples of rock and subsoil from the riverbed to the south of South Street and north of the Shieldhall waste water treatment works.
The information will create a profile of the depth of the river bed and the geological conditions around Glasgow as part of the widespread investigation.
In addition, a small boat will use radar to survey parts of the Clyde to identify any obstructions and there will be further site investigations on land near the north bank.
That work will involve the drilling of boreholes at various locations near Partick Pumping Station, Clydeside Express-way, Castlebank Street, South Street and Clydeholm Road.
This work will establish ground conditions for the location of services in these areas.
Work is expected to be completed by about the end of next month or early June.
Mark Maclaren, Scottish Water's regional communities team manager, said: "We will do everything possible to minimise any inconvenience to residents, road-users and businesses in the area.
"Our work will require some road traffic management and work in verges adjacent to residential areas.
"We will engage with customers in advance of the work."
Meanwhile, in Hamilton, around 2.2km of pipes are set to be improved in a bid to boost water quality.
The £530,000 project begins around May 1 and will take place in Union Street and at its junction of Almada Street.
Work will also take place in Hope Street, Park Road and Orchard Street.