Multi-modal chemical sensors based on microelectromechanical systems (MEMS) have been developed with an electrical readout. Opto-calorimetric infrared (IR) spectroscopy, capable of obtaining molecular signatures of extremely small quantities of adsorbed explosive molecules, has been realized with a microthermometer/microheater device using a widely tunable quantum cascade laser. A microthermometer/microheater device responds to the heat generated by nonradiative decay process when the adsorbed explosive molecules are resonantly excited with IR light. Monitoring the variation in microthermometer signal as a function of illuminating IR wavelength corresponds to the conventional IR absorption spectrum of the adsorbed molecules. Moreover, the mass of the adsorbed molecules is determined by measuring the resonance frequency shift of the cantilever shape microthermometer for the quantitative opto-calorimetric IR spectroscopy. In addition, micro-differential thermal analysis, which can be used to differentiate exothermic or endothermic reaction of heated molecules, has been performed with the same device to provide additional orthogonal signal for trace explosive detection and sensor surface regeneration. In summary, we have designed, fabricated and tested microcantilever shape devices integrated with a microthermometer/microheater which can provide electrical responses used to acquire both opto-calorimetric IR spectra and microcalorimetric thermal responses. We have demonstrated the successful detection, differentiation, and quantification of trace amounts of explosive molecules and their mixtures (cyclotrimethylene trinitramine (RDX) and pentaerythritol tetranitrate (PETN)) using three orthogonal sensing signals which improve chemical selectivity.