This paper introduces an optimized oxygen (O₂) plasma surface treatment technique to enhance sphere lithography on hydrophobic photoresist surfaces. The focus is on semiconductor manufacturing, particularly the creation of finer structures beyond the capabilities of traditional photolithography. The key breakthrough is a method that makes substrate surfaces hydrophilic without altering photoresist patterns. This is achieved by meticulously controlling the O₂ plasma treatment duration. The result is the consistent formation of nano and microscale patterns across large areas. From an academic perspective, the study deepens our understanding of surface treatments in pattern formation. Industrially, it heralds significant progress in semiconductor and precision manufacturing sectors, promising enhanced capabilities and efficiency.