Nigeria's healthcare system faces critical dependency on imported histological stains, creating supply vulnerabilities and foreign exchange pressures that limit diagnostic accessibility. This systematic review evaluated the efficacy, cost-effectiveness, and implementation potential of indigenous Nigerian histological stains through a comprehensive synthesis of existing evidence. We conducted searches across six databases (PubMed, Scopus, Web of Science, AJOL, African Index Medicus, and Google Scholar) from 2000 to 2024, identifying reviews that examined locally sourced staining materials within Nigeria's geographical boundaries. Two reviewers independently screened 847 records, extracted data from 42 included reviews, and assessed methodological quality using AMSTAR-2. We performed a mixed-methods synthesis, combining quantitative aggregation and thematic analysis, using R version 4.3.2 and NVivo 14. The reviews documented 98 distinct indigenous staining sources: 78 plant species (80%), 12 animal-derived materials (12%), and eight mineral sources (8%). Comparative efficacy analysis revealed an 81% success rate for connective tissue applications (95% CI: 69-91%), 67% for cytoplasmic staining (95% CI: 52-79%), but only 22% for nuclear staining (95% CI: 12-36%). Indigenous alternatives provided cost reductions of 65-82% compared to imported stains, although quality inconsistency affected 68% of the materials. Implementation rates varied dramatically: 63% in teaching institutions versus 17% in clinical laboratories (χ²(1) = 21.4, p < 0.001). Indigenous Nigerian histological stains represent scientifically viable and economically advantageous alternatives that require systematic standardisation and regulatory frameworks to achieve clinical adoption