Leishmaniasis remains one of the most prevalent neglected tropical diseases, with Leishmania infantum being a major cause of visceral leishmaniasis, a potentially fatal condition if left untreated. Despite advances in vaccine development, no human vaccine is currently licensed, highlighting the urgent need for innovative immunization strategies. Recombinant protein-based vaccines have emerged as promising candidates due to their capacity to induce targeted immune responses. This review synthesizes findings from 30 studies, identified through a systematic search in PubMed, Scopus, and Web of Science (January 2000 to February 2025) following PRISMA guidelines, evaluating recombinant protein vaccines in Leishmania infantum-infected BALB/c mice, with emphasis on vaccine formulations, delivery methods, and immunological outcomes. Most studies employed subcutaneous immunization and saponin-based adjuvants, testing a variety of antigens, including full-length proteins, chimeric constructs, and unique epitopes. Consistently, these vaccines elicited a Th1-skewed immune response marked by elevated IFN-γ, IL-12, and GM-CSF levels, along with a high IgG2a/IgG1 ratio, immunological indicators of effective protection. Significant reductions in parasitic load were observed in key organs such as the liver, spleen, and bone marrow across vaccinated groups. While all constructs demonstrated protective efficacy, none showed clear superiority. Although modern delivery platforms like nanoparticles, liposomes, and polymer-based systems have shown promise in enhancing antigen stability and immunogenicity, their exploration remains limited, signaling a critical research gap. To advance the development of recombinant protein vaccines against Leishmania infantum, future efforts should prioritize the discovery of novel antigens, optimization of adjuvant formulations, and integration of innovative delivery platforms.