This paper discusses the physiological and technological concepts that might form the future of critical care medicine. Initially, we discuss the need for a personalized approach and introduce the concept of personalized physiological medicine (PPM), including (1) assessment of frailty and physiological reserve, (2) continuous assessment of organ function, (3) assessment of the microcirculation and parenchymal cells, and (4) integration of organ and cell function for continuous therapeutic feedback control. To understand the cellular basis of organ failure, we discuss the processes that lead to cell death, including necrosis, necroptosis, autophagy, mitophagy, and cellular senescence. In vivo technology is used to monitor these processes. To this end, we discuss new materials for developing in vivo biosensors and drug delivery systems. Such in vivo biosensors will define the diagnostic platform of the future ICU in vivo interacting with theragnostic drugs. In addition to pharmacological therapeutic options, placement and control of artificial organs to support or replace failing organs will be central in the ICU in vivo of the future. Remote monitoring and control of these biosensors and artificial organs will be made using adaptive physiological mathematical modeling of the critically ill patient. The current state of these developments is discussed.