The present chapter focuses on the significance of computational methods in understanding the drugs-polymers interactions- a factor of critical important in formulation design. By utilizing computer assisted simulations would predict and study the behaviour of drugs when they come in contact with several polymers, that insight into formulation stability, release kinetics and enhancement of bioavailability. Computer-assisted simulations such as Monte Carlo method or molecular dynamic enables investigation at molecular level. This would help in the enhanced understanding of how drugs-polymers interact and along with their physicochemical properties of the resulting formulation. The main key aspects covered in this chapter includes polymers selection with respect to chemical characteristics and compatibility nature with specific drugs, structure of polymers with respect to drug encapsulation efficiency, and the impact of drug-polymer interactions on formulation performance results. Examples and case studies will be used to demonstrate how computational techniques/ methods guide experimental design, optimize formulation parameters and leads to development of effective drug delivery systems. This chapter has emphasized on computational methods/ tools that improves formulation predictability, accelerate drug development process and support rational design. By utilizing computer-assisted simulations provides guidance to researchers about drug-polymer complexities and open up a pathway for development of new pharmaceutical product with enhanced therapeutic outcomes.