A method and system for cache injection using clustering are provided. The method includes receiving an input/output (I/O) transaction at an input/output device that includes a system chipset or input/output (I/O) hub. The I/O transaction includes an address. The method also includes looking up the address in a cache block indirection table. The cache block indirection table includes fields and entries for addresses and cluster identifiers (IDs). In response to a match resulting from the lookup, the method includes multicasting an injection operation to processor units identified by the cluster ID.