The South African sensation will again line up against former world champions Yohan Blake of Jamaica and American Tyson Gay in the five-lane 100m race in Boston’s Charles Street.
Simbine finally got one over Blake, who is second on the world all-time list with his personal best of 9.69 seconds, at the Gold Coast Commonwealth Games last month.
Blake has had the South African’s number finishing ahead of him at both the Rio 2016 Olympic Games and 2017 IAAF World Championships 100m finals.
Simbine boasts the fifth fastest time this season with his Commonwealth Games winning time of 10.03.
The race will include Great Britain’s Zharnel Hughes with a season’s best of 10.01 with Trinidad and Tobago’s Keston Bledmon completing the draw.
Simbine will be joined in Boston by compatriot Dominque Scott-Efurd racing in the 1500m.
This will be Scott-Efurd’s first competitive race since she joined Joe Bosshard’s training group which includes world 3000-metre steeplechase champion Emma Coburn of the United States.
Scott-Efurd last lined up against 1500m record-holder Caster Semenya at the Athletix Grand Prix meeting in Paarl in March.
She clocked a season’s best of 4:08.61 finishing behind Semenya to fall 0.57s short of her personal best.
The South African will line up against Ethiopia’s 2016 world indoor medalists Dawit Seyaum and Gudaf Tsegay.
Meanwhile, former world 200m bronze medallist Anaso Jobodwana will open his international campaign in the IAAF World Challenge series opener at the Jamaica International Invitational Meeting today.
Jobodwana will line up against two-time world 400m champion LaShawn Merritt of the United States and Commonwealth Games silver medallist Aaron Brown of Canada in the half-lap sprint.
The South African will be looking to make up for the false start debacle at the Commonwealth Games where he missed out on the 200m final.
He false started in the semi-final but was allowed to race only to be disqualified retroactively. It will also be Jobodwana’s first race since he moved back to the United States to join up with his wife and first-born child.
Jobodwana boasts the eighth fastest time this season with the 20.07 he clocked in Paarl in March.