This study aimed to evaluate the performance and effectiveness of two water-soluble transition metal salts, nickel acetate and iron oxalate, in upgrading extra-heavy crude oil from Cuba. The experiment involved treating Cuba oil with water and each catalyst in an autoclave reactor under reservoir conditions for 24 h at 300 °C. Various analyses were conducted to assess the catalyst performance in reducing the viscosity of the crude oil, including gas chromatography (GC) of evolved gases, viscosity, and SARA analysis, elemental analysis, and GC analysis of saturated hydrocarbons. The results showed that both catalysts were able to significantly reduce the Cuba oil’s viscosity, with nickel acetate exhibiting a higher reduction of 80% from 16 420 to 3630 mPa·S, compared to iron oxalate, which showed a reduction of 69% from 16 420 to 5200 mPa·S. A significant decrease in asphaltenes was observed after the upgrading process with nickel acetate, with the content decreasing from 20.86 to 12.85%. Furthermore, the study conducted transformation analyses on the catalysts, both before and after the upgrading process, utilizing TG-FTIR analysis, XRD analysis, Mössbauer studies, and SEM-EDX analysis. These analyses revealed that nickel acetate had the advantage of desulfurization through hydrodesulfurization reactions, indicating its capability of reducing the sulfur content of the oil. The SEM-EDX results showed that the sulfur content formed on the nickel metal after the reaction was 16.21%, while the sulfur content formed on the surface of the iron metal constituted only 2.33%. The XRD results also showed large quantities of α-NiS, β-NiS, and Ni3S4 crystals formed after the reaction, in contrast to iron oxalate, which after the reaction formed large quantities of Fe3O4 (magnetite). This finding underscores the importance of nickel acetate in achieving the objectives of the upgrading process. In summary, the study highlights the potential of water-soluble catalysts, such as nickel acetate and iron oxalate, in upgrading heavy crude oil and reducing its viscosity. Moreover, the study emphasizes the importance of understanding the properties of the catalysts and their transformations during the upgrading process.