Background: Cross-border movements, especially from a malaria-endemic neighbour, contribute to importation of malaria, as they provide favourable conditions for malaria transmission in the receiving country. In the KwaZulu-Natal (KZN) province of South Africa (SA), the uMkhanyakude district is one of the endemic malaria areas where the borders are characterised by frequent cross-border movements of travellers coming into the province, mostly from Mozambique. Many studies have suggested that regional efforts through the implementation of cross-border measures are needed in both the high- and low-endemic countries to effectively address imported malaria. The implementation of cross-border measures to prevent imported malaria has led to a significant decline in malaria cases in KZN and SA; however, those measures are subjected to various challenges. Objective: This study sought to determine the health system challenges of implementing cross-border preventive measures for imported malaria at the Kosi Bay, Kwaphuza and Golela ports of entry in KZN. Methods: This inquiry consisted of a mixed methods approach, of which the qualitative component is reported here. In-depth interviews were conducted with four purposively selected health officers working at the legal and illegal ports of entry of the KZN province. Data were coded manually and then analysed using thematic data and descriptive analyses. Results: This study identified operational and prevention challenges. The related operational challenges included travellers' non-disclosure and refusal, uncontrolled cross-border movements and poor coverage as well as shortage of staff. The prevention challenges included lack of novelty in the existing cross-border preventive measures, insecurity and illegal migration. Concerning travellers' non-disclosure and refusal to cooperate, these issues occur at the legal ports of entry of Kosi Bay and Golela, where travellers were less cooperative in disclosing their health-related information to health border officers. They were more eager to cross and attend to their business. The findings revealed a lack of new ideas in the existing cross-border measures for the prevention of imported malaria, which some scientists considered as the reason for the failure of the elimination efforts in SA. Because of the porous borders and the shortage of staff to cover all the uncontrolled entries, travellers constantly crossed without any hindrances. Porous borders exposed the people living at the border areas and travellers to insecurity, promoted criminal activities and encouraged illegal migration. Conclusion: Cross-border malaria preventive measures are meant to contribute to decreased travel-related disease. Failure to attain this purpose must be carefully examined and mitigation strategies implemented. The study revealed the challenges of implementing cross-border measures at the KZN ports of entry of Kosi Bay, Kwaphuza and Golela. The challenges occurred at the operational and prevention levels, which, if not effectively addressed, could impede the decrease of imported malaria in the malaria-endemic district of KZN and SA in general.