The combustion of hydrocarbons will continue to feed the planet's growing demand for mobility and power generation over the next several decades, shifting to lower value, more difficult-to-burn fuels while at the same time meeting more stringent emissions regulations. These lower-value fuels include heavy fuel oils and vacuum residuals, which are difficult to burn cleanly due to the presence of asphaltenes, the exceptionally high molecular weight insoluble fractions found in high concentrations in crude oils. In particular, heavy fuel oils (HFO) are widely used fuels in marine and power-generation sectors, and International Maritime Organization's (IMO2020) promulgation has redistributed the HFO demand and pushed the world's economy into a new paradigm. We seek solutions for such a complex oil industry paradigm utilizing some state-of-the-art technologies like ultrasonically induced (UIC) cavitation. In the current chapter, we have discussed a roadmap for use of "bottom-of-barrel fuel" with high asphaltene content via UIC-based fuel upgrading, desulfurization, and direct use (emulsions). We expect that a strategy of using UIC for asphaltene modification and water-in-HFO-enabled micro-explosions will significantly impact the combustion of HFO. Furthermore, ultrasonic-assisted oxidative desulfurization (UAOD) can be utilized to remove undesired sulfur to meet marine or power sector requirements. Applications of deasphalting, emulsions, and desulfurization solutions could be for a multiplicity of combustion-driven energy conversion platforms, including compression ignition engines, gas turbines, and boilers.