Multi-parameter real-time profiling of biological and chemical molecules and reactions provides important insights into their mechanisms of action, which serves as the first step to further advance in bioscience and bioengineering. Compared with bulky laboratory solutions, CMOS technologies allow massive integration of different sensor modalities, including optical, electrical, ultrasound, mechanical, etc., onto a single mm-sized sensing platform. This lab-on-CMOS concept is advantageous in probing the biomolecular processes with high sensitivity and specificity in a quantitative way. This work explores the design of a hybrid microwave and optical biomolecular sensor in 28nm CMOS process. The microwave sensing unit is a superharmonic coupled QVCO (quadrature voltage controlled oscillator) for permittivity detection which achieves label/reference-free 5.4ppm 8-hour stability. The optical sensing unit is an SPAD (single photon avalanche diode) array for photon counting and fluorescent lifetime measurements. Experiments on enzyme denaturation under thermal and chemical stress are performed to demonstrate the benefits of this multi-parametric lab-on-CMOS sensing solution.