An Information Handling System (IHS) includes at least one node provisioned with heat-generating components and an air passage that enables air to pass through the node and exit the node as exhaust air. An air-to-liquid heat exchanger (ATLHE) block is placed in a path of the exhaust air. The ATLHE block has an air directing structure, one or more air movers to move the exhaust air through the air directing structure, and an ATLHE. The ATLHE includes a liquid transfer conduit having at least one liquid supply port extending into a heat transfer section, which terminates into at least one liquid return port, the liquid transfer conduit enabling cooling liquid transfer through the ATLHE. A liquid cooling subsystem includes supply and return conduits. The supply conduit is sealably mated to the at least one supply port and the return conduit is sealably mated to the at least one return port.