The objective of this study was to ascertain the elements that influence the effectiveness of mathematics instruction in the 21st century for secondary school students within the jurisdiction of the secondary educational service area office Lopburi (SEAOL). The research utilized survey methodology. The study population consisted of 400 secondary school students from SEAOL during the first semester of 2022. The participants were selected using a stratified random selection technique. The research tool utilized in this study was a questionnaire, which demonstrated a high level of reliability with a coefficient of 0.934. The research employed principal component analysis as the statistical analysis approach. The findings of the study indicate that there are various factors that influence the effectiveness of mathematics instruction in the 21st century for secondary school students in SEAOL. These factors include the level of technology support from schools, use of technology, ability to use basic technology, ability to use specialized technology, knowledge of content, math is crucial, and variety of teaching methods. Additionally, the study reveals that gender, program, and education level have a significant impact on knowledge and opinions regarding mathematics instruction, with statistical significance observed at a significance level of 0.05.