Spurs' 10th manager in 13 years begins their Premier League season with a London derby at Upton Park as they again go in pursuit of a top-four finish.
Both Andre Villas-Boas and Tim Sherwood fell victim to trigger-happy Lillywhites chairman Daniel Levy last campaign as the club struggled to overcome the loss of the world's most expensive player - Gareth Bale.
Their £110m worth of summer signings largely failed to deliver and now Pochettino has been lured from Southampton to inspire Tottenham's talented, but unbalanced, squad to Champions League qualification.
There is also the sense of a fresh start at West Ham, with manager Sam Allardyce having been instructed to deliver the attractive football that was apparently lacking as they comfortably survived last term.
Allardyce has appointed former White Hart Lane favourite Teddy Sheringham as an attacking coach to try to aid this transition, but will have to start the campaign without his two main strikers.
O'Brien could be joined in defence by two new recruits, left-back Aaron Cresswell and £7m centre-half Cheikhou Kouyate, while the skilful Mauro Zarate could make his debut on the wing. Diego Poyet may have to settle for a place on the bench against a side for whom father Gus made 98 appearances.
With Tottenham's World Cup contingent having only recently returned to pre-season training, and up to 11 players reportedly available for transfer, Pochettino's maiden team selection will make for interesting reading.
Nacer Chadli, Moussa Dembele and Paulinho may not yet be up to match sharpness, but Belgian international Jan Vertonghen could be rushed back to compensate for injuries to Michael Dawson and Vlad Chiriches.
Either Younes Kaboul or Eric Dier, one of three new recruits who will be in the squad, will partner Vertonghen, while left-back Ben Davies should make his Spurs bow after joining for £10m from Swansea City.
His former Liberty Stadium teammate Michel Vorm, will likely play second fiddle to Hugo Lloris, who signed a new contract with Spurs in July, in goal. Kyle Naughton should stand in for Kyle Walker at right-back, with the 24-year-old still recovering from the pelvic injury that ruled him out of Brazil 2014.
Erik Lamela is expected to get a run in the team after enduring a difficult first season in England following his £30m move from Roma, and there could also be starts for Lewis Holtby, who impressed during pre-season games, and Roberto Soldado, with Emmanuel Adebayor having recently suffered from malaria.
Possible starting lineups
West Ham: Adrian; O'Brien, Reid, Kouyate, Cresswell; Diame, Noble, Nolan; Downing, Zarate; Cole
Spurs: Lloris; Naughton, Kaboul, Vertonghen, Davies; Bentaleb, Sandro; Eriksen, Holtby, Lamela; Soldado
Sports Mole says: 1-1