The 'Philadelphia' actor will portray award-winning journalist Mike McAlary in the play, which has been written by late Academy Award nominee Nora Ephron.
The production charts the career highs and lows of the controversial tabloid reporter, who won the Pulitzer Prize in 1998 for his coverage on the police brutalisation of Abner Louima and died from colon cancer later that year.
Two-time Tony Award winner George C. Wolfe is to direct the play, which will begin previews at the Broadhurst Theatre on March 1 2013, with the official opening night slated for April 1.
'Lucky Guy' marks Tom's first stage performance since 1979, when he performed with the Riverside Shakespeare Company in New York.
The play had been in doubt following the death of Nora - who also wrote Tom's films 'Sleepless in Seatle' and 'You've Got Mail' - in June.
Further casting information will be released in the coming weeks.