Instead of using an external filter that expands macros, one way to do things is to write programs that write part or all of other programs.
For instance, you could use a program outputting source code
to generate sine/cosine/whatever lookup tables,
to extract a source-form representation of a binary file,
to compile your bitmaps into fast display routines,
to extract documentation, initialization/finalization code, description tables, as well as normal code from the same source files,
to have customized assembly code, generated from a perl/shell/scheme script that does arbitrary processing,
to propagate data defined at one point only into several cross-referencing tables and code chunks.
etc.
Think about it!
Compilers like GCC, SML/NJ, Objective CAML, MIT-Scheme, CMUCL, etc, do have their own generic assembler backend, which you might choose to use, if you intend to generate code semi-automatically from the according languages, or from a language you hack: rather than write great assembly code, you may instead modify a compiler so that it dumps great assembly code!
There is a project, using the programming language Icon (with an experimental ML version), to build a basis for producing assembly-manipulating code. See around http://www.eecs.harvard.edu/~nr/toolkit/
The TUNES Project for a Free Reflective Computing System is developing its own assembler as an extension to the Scheme language, as part of its development process. It doesn't run at all yet, though help is welcome.
The assembler manipulates abstract syntax trees, so it could equally serve as the basis for a assembly syntax translator, a disassembler, a common assembler/compiler back-end, etc. Also, the full power of a real language, Scheme, make it unchallenged as for macroprocessing/metaprogramming.