One of the main goals in metagenomics is to identify the functional profile of a microbial community from unannotated shotgun sequencing reads. Functional annotation is important in biological research because it enables researchers to identify the abundance of functional genes of the organisms present in the sample, answering the question, “What can the organisms in the sample do?” Most currently available approaches do not scale with increasing data volumes, which is important because both the number and lengths of the reads provided by sequencing platforms keep increasing. Here, we present SUPER-FOCUS, SUbsystems Profile by databasE Reduction using FOCUS, an agile homology-based approach using a reduced reference database to report the subsystems present in metagenomic datasets and profile their abundances. SUPERFOCUS was tested with real metagenomes, and the results show that it accurately predicts the subsystems present in the profiled microbial communities, is computationally efficient, and up to 1000 times faster than other tools. SUPER-FOCUS is freely available at http://edwards.sdsu.edu/SUPERFOCUS.