Goals from Ghana captain Thomas Partey and debutant Emmanuel Boateng with a penalty ensured a miserable night for Nishino and means the ex-Japan midfielder has difficult decisions to make in the next 24 hours before naming his 23-man World Cup squad.
Nishino, who took over from Vahid Halilhodzic in April after the Bosnian had guided Japan to next month's finals in Russia, switched the formation with three central defenders, two wing-backs and two inside forwards supporting a lone striker.
Despite wing backs Yuto Nagamoto and Genki Haraguchi posing a threat going forward, there was confusion in defence with the back three often sitting too deep and Haraguchi caught out of position at least three times in the first half.
Partey scored with a free-kick after eight minutes as Nishino’s new formation failed to function with brief moments of attacking menace tempered by vulnerability in defence.
Five minutes after the break Japan's back three dawdled and hesitant goalkeeper Eiji Kawashima gave away the spot kick that was coolly dispatched by Boateng for Ghana’s second.
Nishino said there were positives from the game but added that his formation did not work against the pacey Ghana attack.
"I was surprised with the condition of the Ghana players, who managed to switch from defence to attack quickly. As Ghana's reaction was so good, I was not able to use the three at the back as I thought," said Nishino.
"The back three is not a fixed formation. I tried the three at the back to see how we would respond during the game when we were pushed back."
Going forward, Keisuke Honda looked the most likely to score in the first half, twice testing goalkeeper Richard Ofori but the 31-year-old, now plying his trade in Mexico at Pachuca, notably tired in the second half before being substituted.
Shinji Kagawa also looked sharp after coming on at halftime. The Borussia Dortmund playmaker, who has been sidelined with a series of ankle injuries this year, immediately brought more dynamism and creativity to the Japanese attack.
However, it was ultimately a poor night for Nishino, who must now decide on his squad on Thursday with few positives to reflect on from his sole game in charge.
Japan’s first Group H match is against Colombia on June 19 before they face Senegal and Poland at the finals.
(Reporting by Jack Tarrant; Editing by Ken Ferris)
