diff --git a/Formula/sortmerna.rb b/Formula/sortmerna.rb
index 12d3f6da0..e00c4d7c1 100644
--- a/Formula/sortmerna.rb
+++ b/Formula/sortmerna.rb
@@ -2,10 +2,10 @@ class Sortmerna < Formula
   # cite Kopylova_2012: "https://doi.org/10.1093/bioinformatics/bts611"
   desc "Filter metatranscriptomic ribosomal RNA"
   homepage "https://bioinfo.lifl.fr/RNA/sortmerna/"
-  url "https://github.com/biocore/sortmerna/archive/refs/tags/2.1b.tar.gz"
-  sha256 "b3d122776c323813971b35991cda21a2c2f3ce817daba68a4c4e09d4367c0abe"
+  url "https://github.com/biocore/sortmerna/archive/refs/tags/v6.0.2.tar.gz"
+  sha256 "f2a9d2b1a1041436d06278dd147cfa048d027e45edf79c994a80c64fc375e20b"
   license "GPL-3.0"
-  head "https://github.com/biocore/sortmerna.git"
+  head "https://github.com/biocore/sortmerna.git", branch: "master"
 
   bottle do
     root_url "https://ghcr.io/v2/brewsci/bio"
@@ -13,18 +13,65 @@ class Sortmerna < Formula
     sha256 cellar: :any_skip_relocation, x86_64_linux: "b412dde11f5cb06f8c4a1aa3d78719d0647ffe5a2e9ff81df960903346269bd1"
   end
 
+  depends_on "cmake" => :build
+  depends_on "concurrentqueue"
+  depends_on "parasail"
+  depends_on "rocksdb"
+
   uses_from_macos "zlib"
 
+  # Header-only minimal perfect hash function (BBHash/BooPHF), fetched by the
+  # upstream build into 3rdparty/bbhash.
+  resource "bbhash" do
+    url "https://github.com/rizkg/BBHash.git",
+        revision: "be4220c8f8580299b212a0c6c6c867528a0f07ac"
+  end
+
+  # Header-only rapidgzip library (seekable parallel gzip decompression),
+  # fetched by the upstream build into 3rdparty/indexed_bzip2.
+  resource "indexed_bzip2" do
+    url "https://github.com/mxmlnkn/indexed_bzip2.git",
+        revision: "ff5242bf439d996b81ead7fc0d1d9bc2dd0d7a6f"
+  end
+
   def install
-    system "./configure",
-      "--disable-debug",
-      "--disable-dependency-tracking",
-      "--disable-silent-rules",
-      "--prefix=#{prefix}"
-    system "make", "install"
+    # Stage the header-only dependencies where CMake expects them. The upstream
+    # setup.py orchestrator clones these into 3rdparty/ before configuring.
+    (buildpath/"3rdparty/bbhash").install resource("bbhash")
+    (buildpath/"3rdparty/indexed_bzip2").install resource("indexed_bzip2")
+
+    # rocksdb's public headers (compression_type.h) use C++20 features such as
+    # defaulted operator==, so sortmerna must compile as C++20. The CMakeLists
+    # files hardcode `set(CMAKE_CXX_STANDARD 17)`, which shadows a -D flag, so
+    # bump the sources directly.
+    inreplace ["CMakeLists.txt", "src/sortmerna/CMakeLists.txt"],
+              "set(CMAKE_CXX_STANDARD 17)", "set(CMAKE_CXX_STANDARD 20)"
+
+    # sortmerna 6.0.2 targets rocksdb 7.10.2, but Homebrew ships rocksdb >= 9,
+    # which removed the raw-pointer `DB::Open(Options, name, DB**)` overload in
+    # favour of `DB::Open(Options, name, std::unique_ptr<DB>*)`. Adapt the single
+    # call site: open into a unique_ptr, then release into the raw member.
+    inreplace "src/sortmerna/kvdb.cpp",
+              "rocksdb::Status s = rocksdb::DB::Open(options, kvdbPath, &kvdb);",
+              "std::unique_ptr<rocksdb::DB> kvdb_uptr; " \
+              "rocksdb::Status s = rocksdb::DB::Open(options, kvdbPath, &kvdb_uptr); " \
+              "kvdb = kvdb_uptr.release();"
+
+    args = %W[
+      -DWITH_TESTS=OFF
+      -DROCKSDB_USE_STATIC_LIBS=ON
+      -DROCKSDB_DIST=#{formula_opt_prefix("rocksdb")}
+      -DPARASAIL_DIST=#{formula_opt_prefix("parasail")}
+      -DCONCURRENTQUEUE_HOME=#{formula_opt_include("concurrentqueue")}/concurrentqueue/moodycamel
+      -DINDEXED_BZIP2_HOME=#{buildpath}/3rdparty/indexed_bzip2/src
+    ]
+
+    system "cmake", "-S", ".", "-B", "build", *args, *std_cmake_args
+    system "cmake", "--build", "build"
+    system "cmake", "--install", "build"
   end
 
   test do
-    system "#{bin}/sortmerna", "--version"
+    system bin/"sortmerna", "--version"
   end
 end