Wireless power transfer (WPT) systems with Domino repeater arrays can be used to transfer power through complicated structures and extend the effective transfer range. This paper explored a hybrid active/passive Domino architecture with multi-input multi-output (MIMO) power flow control and mixed-frequency operation. By designing and optimizing the circuits and the control methods, the hybrid active/passive Domino architecture can achieve higher efficiency and higher power transfer capability than a passive domino architecture. The hybrid Domino architecture significantly expands the control degree-of-freedom by enabling multi-way power combining and multi-frequency wireless power transfer. The hybrid Domino architecture also enables the high performance multi-layer multimedium wireless power transfer by combining different control strategies. A prototype hybrid Domino WPT system with ten resonators is built and tested to verify the effectiveness of the approach. The prototype delivered 12 W of power from the source and buffer to the load (56% from the source, and 44% from the buffer) with 40% weighted effective efficiency. The endto-end power transfer distance (22 cm) is more than 4 times of the resonator diameter (5 cm). Another experimental setup is built with two transfer mediums (i.e., chicken breast and salt water) to validate the multi-layer multi-medium power transfer capability of the hybrid Domino architecture, where one active resonator is placed at the interface of the two mediums. The hybrid Domino WPT system can delivery 30% more power than a passive Domino system in the multi-medium WPT experiments.