A Translation Lookaside Buffer (TLB) is a memory cache that improves access speed by storing recent translations of virtual memory to physical addresses, which helps avoid multiple memory accesses. It operates by checking for virtual page numbers, resulting in either a TLB hit (found in cache) or a TLB miss (not found, requiring additional lookups). Handling TLB misses can involve either hardware or software methods to retrieve the necessary data and manage page faults effectively.