To monitor health risks associated with vaping, we introduce a multi-spectral optical sensor powered by machine learning for real-time characterization of electronic cigarette aerosols. The sensor can accurately measure the mass of particulate matter (PM) in specific particle size channels, providing essential information for estimating lung deposition of vaping aerosols. For the sensor’s input, wavelength-specific optical attenuation signals are acquired for three separate wavelengths in the ultraviolet, red, and near-infrared range, and the inhalation pressure is collected from a pressure sensor. The sensor’s outputs are PM mass in three size bins, specified as 100–300 nm, 300–600 nm, and 600–1000 nm. Reference measurements of electronic cigarette aerosols, obtained using a custom vaping machine and a scanning mobility particle sizer, provided the ground truth for size-binned PM mass. A lightweight two-layer feedforward neural network was trained using datasets acquired from a wide range of puffing conditions. The performance of the neural network was tested using unseen data collected using new combinations of puffing conditions. The model-predicted values matched closely with the ground truth, and the accuracy reached 81–87% for PM mass in three size bins. Given the sensor’s straightforward optical configuration and the direct collection of signals from undiluted vaping aerosols, the achieved accuracy is notably significant and sufficiently reliable for point-of-interest sensing of vaping aerosols. To the best of our knowledge, this work represents the first instance where machine learning has been applied to directly characterize high-concentration undiluted electronic cigarette aerosols. Our sensor holds great promise in tracking electronic cigarette users’ puff topography with quantification of size-binned PM mass, to support long-term personalized health and wellness.