This retrospective comparative study aimed to conduct an in-depth analysis of malaria prevalence trends in Kanungu District, Uganda between the years 2020 to 2024 in order to gain a comprehensive understanding of the disease burden over time, persistent challenges hampering optimal control efforts, and recommend strategic interventions to accelerate progress towards national targets. A mixed methods sequential explanatory research design was employed incorporating review of routinely collected malaria case surveillance data as well as qualitative inquiries to capture diverse stakeholder perspectives at the community, health facility and district levels. Quantitative descriptive analyses examined annual fluctuations in caseloads and their distribution according to age, sex and location while qualitative thematic analyses uncovered grassroots operational realities. Triangulating epidemiological patterns with explanatory themes revealed socioeconomic and health systems determinants necessitating reformed approaches. The generated evidence-based insights offer the Kanungu District malaria control program an empirically grounded basis from which to systematically strengthen interventions through multi-sectoral coordination, community participation and continuous monitoring oriented around protecting vulnerable groups disproportionately affected. A coefficient of 0.869 shown a very high linear correlation between higher malaria prevalence and lower wealth quintiles. The significance value of 0.000 confirmed that this correlation was highly unlikely to have occurred by chance, given that the p-value is less than 0.01. Promote integrated vector management embracing environmental management strategies including draining of mining waste pools and stabilization of erosion prone areas in collaboration with relevant district departments to curb breeding habitats and reduce re-infestation risks over the long-term.