Is there a way to make this work?

I find that mucking around with the symbol table like this with persistent test environments is just more trouble than it's worth. Maybe try using Hook::LexWrap instead?

use strict;
use warnings;

{   package X;
    use base qw(Test::Class);
    use Test::More;
    use DateTime;
    use Hook::LexWrap;
    
    sub setup_test_double : Test( startup ) {
        my ( $self ) = @_;
        # we stick our Hook::LexWrap object in $self so it'll 
        # magically go out of scope after this test class has
        # run, so get garbage collected, so return DateTime to
        # its pristine state
        $self->{ test_double } 
            = wrap 'DateTime::now', pre => sub { $_[-1] = 'XXXX' };
    }
    
    sub use_test_double : Test {
        my ( $self ) = @_;
        is( DateTime->now, 'XXXX' );
    }
    
}

{   package Y;
    use base qw(Test::Class);
    use Test::More;
    use DateTime;
    
    sub using_real_class : Test {
        my ( $self ) = @_;
        isa_ok( DateTime->now, 'DateTime' );
    }
}

Test::Class->runtests;
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