Genetics-based neuromodulation schemes are capable of selectively manipulating the activity of defined cell populations with high temporal-spatial resolution, providing unprecedented opportunities for probing cellular biological mechanisms, resolving neuronal projection pathways, mapping neural profiles, and precisely treating neurological and psychiatric disorders. Multimodal implementation schemes, which involve the use of exogenous stimuli such as light, heat, mechanical force, chemicals, electricity, and magnetic stimulation in combination with specific genetically engineered effectors, greatly expand their application space and scenarios. In particular, advanced wireless stimulation schemes have enabled low-invasive targeted neuromodulation through local delivery of navigable micro- and nanosized stimulators. In this review, the fundamental principles and implementation protocols of genetics-based precision neuromodulation are first introduced.The implementation schemes are systematically summarized, including optical, thermal, force, chemical, electrical, and magnetic stimulation, with an emphasis on those wireless and low-invasive strategies. Representative studies are dissected and analyzed for their advantages and disadvantages. Finally, the significance of genetics-based precision neuromodulation is emphasized and the open challenges and future perspectives are concluded.