The growing demand for heavy oil and bitumen stresses the need for advanced upgrading technologies to overcome the challenges of high viscosity, low API gravity, and asphaltene instability. Asphaltenes, the most polar and complex fraction of crude oil, govern the physicochemical behavior of these resources, yet their aggregation and precipitation cause major flow and processing issues. This review critically examines the role of nanoparticles as adsorptive and catalytic agents for asphaltene mitigation and bitumen upgrading, integrating mechanistic understanding with practical strategies to enhance efficiency and sustainability. It first revisits the fundamental principles of asphaltene chemistry, molecular structure, thermodynamic behavior, and aggregation-deposition mechanisms, followed by current mitigation approaches. Then, the evolution of nanoparticle research is analyzed, highlighting the molecular and interfacial mechanisms by which nanoparticles adsorb, destabilize, and catalytically convert asphaltenes. Particular focus is given to transition metal oxides and sulfides, whose tunable acid–base and redox properties enable C–C and C–S bond cleavage, heteroatom removal, and hydrogen transfer reactions that yield lighter, more stable hydrocarbons. Both in situ and ex situ upgrading strategies are reviewed with respect to their operating principles, performance, and technoeconomic implications. Advances in computational modeling across molecular to continuum scales are also discussed, offering insights into reaction kinetics, particle transport, and coupled heat and mass transfer. The review concludes by outlining challenges in nanoparticle stability, deactivation, and scalability, and emphasizes intelligent catalyst design and life-cycle assessment as key to achieving sustainable heavy oil upgrading and recovery.