Malaria is a life-threatening but preventable disease caused by Plasmodium parasites transmitted through bites of infected female Anopheles mosquitoes. According to the World Health Organization, the Western Pacific Region reported 1.7 million malaria cases in 2023, of which Plasmodium vivax accounted for 28.9% of cases and approximately 3500 malaria-related deaths. This reflects a decrease in the incidence of malaria cases and associated mortality compared to 2022, highlighting progress but underscoring persistent challenges. Cambodia, with its goal to eliminate malaria by 2025, continues to face public health challenges, particularly from P. vivax and mixed-species infections. This report provides an in-depth epidemiological analysis of malaria cases and radical cure treatment outcomes for P. vivax and mixed-species infections in Kampong Speu Province from 2019 to 2023. Data were drawn from Cambodia’s national Malaria Information System and radical cure treatment records. The analysis demonstrated a substantial increase in malaria screening, primarily conducted by village malaria workers, while the number of confirmed malaria cases continued to decline. The annual parasite incidence dropped from 23.8 per 1000 at-risk individuals in 2019 to 0.7 per 1000 in 2023. Radical cure treatment completion rates among eligible cases improved from 78% in 2019 to 98% in 2023. Significant progress has been made towards malaria elimination. However, males aged 15–49 years, particularly forest-goers in the Kampong Speu operational district, remain the most at-risk group. In support of malaria elimination, it is recommended to enhance prevention measures, increase screening and ensure 100% radical cure treatment for all eligible cases in high-risk populations.