This study presents a deterministic model developed to examine how malaria drug resistance and various preventive strategies influence the transmission dynamics of malaria–typhoid fever co-infection. The model introduces additional compartments to account for individuals simultaneously infected with drug-resistant malaria and typhoid fever, and it considers their role in propagating the diseases. Numerical simulations suggest that preventing drug-resistant malaria significantly reduces the spread of malaria–typhoid co-infections within the population. Furthermore, cost-effectiveness analysis indicates that the most efficient intervention among the strategies examined is one that targets the prevention of typhoid fever from both bacterial sources and human carriers. This combined approach offers the greatest reduction in disease burden at the lowest cost.