The present disclosure relates generally to systems and methods for transmitter leak-over cancellation. In one example, a method includes transmitting a signal via a transmit chain in a wireless device, where a portion of the signal leaks over into a receive chain of the wireless device. A portion of the signal is diverted from the transmit chain into cancellation circuitry coupled to the receive chain to manipulate an amplitude and phase of the portion before combining the manipulated portion with the signal and other portion to at least partially cancel interference caused by the leak-over portion. After downconverting, a remainder portion is filtered from the received signal. A power level of the remainder portion is detected and compared to a threshold value. An amplitude and phase configuration of the cancellation circuitry is modified based on a result of comparing the power level to the threshold value.