Malaria remains one of the most persistent global health challenges, with climate change, vegetation changes, and migration playing a critical role in shaping its spatial dynamics. The chapter explores malaria case dynamics and potential risk transmission in relation to climate change, migration, and vegetation change in the Eastern Cape Province in South Africa. A literature review was conducted across three databases (Medline, Pubmed, and Google Scholar), as well as the grey literature for research papers and reports. Data were analyzed qualitatively. A total of 80 studies were selected for the review based on specific eligibility criteria. The review highlighted the relationship between climate change, bush encroachment, human mobility, and mostly imported cases of malaria in the Eastern Cape Province. However, there was little information to highlight the early onset of an unstable malaria transmission. There is no proven malaria transmission in the Eastern Cape Province in South Africa. Nonetheless, imported cases of malaria are a public health concern. Understanding the interplay between climate change, migration, vegetation changes, and malaria dynamics is becoming increasingly important for public health interventions.