A vast number of pathological brain conditions directly involve aberrant electrical activity of the brain. CROSSBRAIN centres its technological revolution on the convergence of novel nanoactuation modalities, bleeding-edge nano-electronics, and miniaturized wireless energy harvesting and communication. Combining extreme edge computing with advanced nanomaterials featuring tailored physical properties, biocompatible coatings, and material modifications to prevent glial scarring, CROSSBRAIN will enable individualized, adaptive and highly spatiotemporally localized actuation of brain tissue. It will leverage sensing electric local field potentials, multiunit neuronal activity, and cross-modal nanomaterial-based modulation (electrical, mechanical, thermal, ionic concentration, optogenetics) of neuronal excitability with on-board intelligence. The CROSSBRAIN platform comprises a swarm of wireless, implantable, MRI-compatible microbots for in vivo electrophysiology and cross-modal neuromodulation at the cell- and microcircuit levels, in freely moving rodents. CROSSBRAIN delivers a multiplicity of stimulation modalities, involving electro-mechano-magneto-thermo-optical principles for modulation of nerve cell excitability. The microbots will feature both sensing and actuation electrodes, engineered with nanomaterials and viral vectors coatings. They will be implanted endovascularly, deliver genetic material upon command, and operate in federation under the networked control and wireless power supply by a tiny central unit, which can be worn like an internet of things device. CROSSBRAIN will deliver autonomous or manual, closed-loop sensing, prediction, and actuation through combining multiple neuromodulation mechanisms, which will act in a synergistic and dynamic manner to optimally shape stimulation according to individual neuronal firing patterns or clinician’s needs. As case studies, we will explore CROSSBRAIN action in animal models of Parkinson’s Disease and Epilepsy.