Significance Monitoring human organ-on-a-chip systems presents a significant challenge, where the capability of in situ continual monitoring of organ behaviors and their responses to pharmaceutical compounds over extended periods of time is critical in understanding the dynamics of drug effects and therefore accurate prediction of human organ reactions. In this work, we report a fully integrated modular physical, biochemical, and optical sensing platform, interfaced through a fluidics-routing breadboard with a multi–organ-on-a-chip system to achieve in situ, continual, and automated sensing of microenvironment biophysical and biochemical parameters. It is anticipated that our platform technology that is conveniently compatible with existing organ-on-a-chip models will potentially enhance their performance in drug screening by providing a multitude of sensing data not previously available.