documentclass{scrlttr2}

usepackage{textcase}

makeatletter%
renewcommand{subject@format}[1]{MakeUppercase{#1}}
makeatother%

usepackage{blindtext}

begin{document}
  begin{letter}{Recipient}

    setkomavar{subject}{Foo Subject}

    opening{Dear Sir or Madam}

    blindtext

  end{letter}
end{document}

! Class scrlttr2 Error: KOMA-Script variable not defined.

See the scrlttr2 class documentation for explanation.
Type  H <return>  for immediate help.
...

l.16     opening{Dear Sir or Madam}

? ^C! Interruption.
GenericError  ...

`addtokomafont{MakeUppercase}

documentclass[
  subject=titled,
]{scrlttr2}

usepackage{textcase}
usepackage{etoolbox}
usepackage{blindtext}

makeatletter
patchcmd{@subjfield}
  {usekomavar{subject}}
  {MakeUppercase{usekomavarexp{subject}}}
  {}{}
newcommandusekomavarexp[1]{@nameuse{scr@#1@var}}
makeatother

begin{document}

begin{letter}{Recipient}

setkomavar{subject}{Foo Subject}

opening{Dear Sir or Madam}

blindtext

end{letter}

end{document}

setkomavar{subject}{MakeUppercase{Foo Subject}}