The current study aims to investigate cenosphere formation during single-droplet combustion of heavy fuel oil (HFO). A droplet generator was developed to produce freely falling monodisperse droplets uniformly. With the aid of high-speed imaging, droplet diameter was verified to be well controlled within the range of 390-698 μm, and droplets spacing distance was sufficient to avoid droplet-droplet interactions. Impacts of operation conditions (initial HFO droplet size, temperature, and air co-flow rate) and asphaltene content on cenosphere formation in a drop tube furnace were then investigated. Three types of cenosphere morphology were observed by field emission scanning electron microscopy (SEM), namely, larger hollow globules, medium porous cenospheres, and smaller cenospheres with a perfectly spherical and smooth structure. The SEM results show that the mean diameter of collected cenospheres increased as initial droplet size and asphaltene content increased, while it decreased as temperature and air co-flow rate increased. Energy-dispersive X-ray spectroscopy results show that these parameters also significantly influenced the evolution of cenosphere surface elemental composition. All parameters show linear effects on the surface content of C, O, and S, excluding air co-flow rate. The increase of air co-flow temperature enhanced droplet combustion; conversely, larger initial droplet size and asphaltene content inhibited droplet combustion. The nonlinear effect of air co-flow rate indicates that it has an optimum rate for falling droplet combustion, as 90 slpm based on the current experimental setup. Eventually, our study proposed the pathway of cenosphere formation during the HFO droplet combustion.