Your two if statements are incompatible - they can never both be true, so no substitution can happen. Aside from that the code works. Consider:

use strict;
use warnings;

my $HR_wnt = {'res.ldlibrarypath' => 'Flobble=/opt/app/Flobble:'};
my $HR_unx;
my $HR_component;
my $target = 'Flobble';

for my $hashref ($HR_wnt, $HR_unx, $HR_component) {
    for my $id (keys %$hashref) {
        if ($id eq 'res.ldlibrarypath') {
            if ($$hashref{$id} =~ /=\//) {
                $$hashref{$id} =~ s/\/opt\/app\/$target.*?://;
            }
        }
    }
}

print $HR_wnt->{'res.ldlibrarypath'};
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Prints:

Flobble=
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Update actually there is nothing wrong with the two if statements. Bogus comment struck, working sample data supplied, commented code reinstated and sample output corrected.