Electrophysiology and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have high temporal resolution, while optical imaging allows recording of genetically‐defined populations at high spatial resolution. Combining these two modalities for simultaneous large‐scale, multimodal sensing of neural activity across multiple brain regions can be very powerful. Here, transparent, inkjet‐printed electrode arrays with outstanding optical and electrical properties are seamlessly integrated with morphologically conformant transparent polymer skulls. Implanted on transgenic mice expressing the Calcium (Ca²⁺) indicator GCaMP6f in excitatory neurons, these “eSee‐Shells” provide a robust opto‐electrophysiological interface for over 100 days. eSee‐Shells enable simultaneous mesoscale Ca²⁺ imaging and electrocorticography (ECoG) acquisition from multiple brain regions covering 45 mm² of cortex under anesthesia and in awake animals. The clarity and transparency of eSee‐Shells allow recording single‐cell Ca²⁺ signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca²⁺ signals that depend on the behavioral state.