The MCE Sandbox project places the C and header files inside the src folder. There is just the one *.c file, everything else placed in *.h files.

.Inline/          Where Inline::C is configured to cache C object file
+s.

bin/
   algorithm3.pl  Practical sieve based on Algorithm3 from Xuedong Luo
+ [1].

src/
   algorithm3.c   Inline::C code for algorithm3.pl.
   bits.h         Utility functions for byte array.
   output.h       Fast printing of primes to a file descriptor.
   sandbox.h      Header file, includes bits.h, output.h, sprintull.h.
   sprintull.h    Fast base10 to string conversion.
   typemap        Type-map file for Inline::C.
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I pass -I${base_dir}/src for Inline C, inside algorithm3.pl

BEGIN {
   $ENV{PERL_INLINE_DIRECTORY} = "${base_dir}/.Inline";
   mkdir "${base_dir}/.Inline" unless -d "${base_dir}/.Inline";
}

use Inline 'C' => Config =>
   CCFLAGSEX => "-I${base_dir}/src -O3 -fomit-frame-pointer",
   TYPEMAPS => "${base_dir}/src/typemap",
   clean_after_build => 0;

use Inline 'C' => "${base_dir}/src/algorithm3.c";
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Later editing a header file requires removing the cache .Inline folder. Inline C does not know to re-compile due to not checking the *.h time stamps.