The feasibility and utility of wearable 24-h multimodality neuromonitoring during daily activities are demonstrated. We have developed a fourth-generation ambulatory near infrared spectroscopy device, namely NINscan 4. NINscan 4 enables recording of brain function (via cerebral hemodynamics), systemic hemodynamics, electrocardiography, and actigraphy simultaneously and continuously for up to 24 h at 250-Hz sampling rate, during (and with minor restriction to) daily activities. We present initial 24-h human subject test results, with example analysis including (1) comparison of cerebral perfusion and oxygenation changes during wakefulness and sleep over a 24-h period and (2) capturing of hemodynamic changes prior, during and after sudden waken up in the night during sleep. These results demonstrate the first ambulatory 24-h cerebral and systemic hemodynamics monitoring, and its unique advantages including long-term data collection and analysis capability, ability to catch unpredictable transient events during activities of daily living, as well as coregistered multimodality analysis capabilities. These results also demonstrate that NINscan 4’s motion artifact at head movement is smaller than physiological hemodynamic fluctuations during motionless sleep. The broader potential of this technology is also discussed.