The article introduces HUMANn2, a tiered meta'omic search strategy for functional profiling of microbial communities. HUMANn2 combines nucleotide-level alignment against pangenomes with translated search to identify and quantify gene families and pathways at the species level. This approach is faster and more accurate than pure translated search, producing gene family profiles with 89% accuracy compared to 67% for pure translated search. HUMANn2 is applied to synthetic and real-world metagenomes, demonstrating its ability to profile clinal variation in marine metabolism and ecological contribution patterns. The method also enables strain-level functional variation analysis and paired metatranscriptome and metagenome comparisons. HUMANn2's tiered search provides taxonomic stratification of microbial functions, allowing for the quantification of community abundance and assignment to specific contributors. The software is open-source and supports an active user community.The article introduces HUMANn2, a tiered meta'omic search strategy for functional profiling of microbial communities. HUMANn2 combines nucleotide-level alignment against pangenomes with translated search to identify and quantify gene families and pathways at the species level. This approach is faster and more accurate than pure translated search, producing gene family profiles with 89% accuracy compared to 67% for pure translated search. HUMANn2 is applied to synthetic and real-world metagenomes, demonstrating its ability to profile clinal variation in marine metabolism and ecological contribution patterns. The method also enables strain-level functional variation analysis and paired metatranscriptome and metagenome comparisons. HUMANn2's tiered search provides taxonomic stratification of microbial functions, allowing for the quantification of community abundance and assignment to specific contributors. The software is open-source and supports an active user community.