An IO subsystem chassis includes IO modules and IO slots to receive the IO modules inserted from a frontend of a housing, a baseboard disposed within the housing, the baseboard including first connectors corresponding to the IO slots to receive and connect the IO modules. Each of the IO modules can be coupled a server via the backend panel using a cable. Each IO module includes an IO card having a peripheral device mounted thereon and a card holder having a first receiving socket to receive and hold the IO card plugged in vertically and downwardly. The card holder further includes a second connector to engage with or disengage from a corresponding one of the first connectors of the baseboard horizontally, when the IO module is inserted into or removed from a corresponding IO slot from the frontend, without having to removing the housing.