Background: Declined test scores, performances and the increasing difficulty in science concepts among students is one of the major problems in Philippine education. Department of Education surveys found out that one of the subjects where lower test scores are seen is science. However, despite the efforts of the educational sector, difficulties are still arising and the educational sector are still searching for ways and actions to address the problem. Objectives: The objective of this research is to explore the most preferable Pedagogical Content Knowledge as a way of addressing the assessed most difficult science conceptamong the five public secondary schools in Roxas, Isabela, Philippines. Methods: The study utilizes a descriptive-correlational approach in research as it describes and correlates the data gathered from the respondents to establish the basis on finding the most preferable Pedagogical Content Knowledge in addressing the difficulty found among the science concepts. Participants of the research are five (5) teachers and one hundred fifty (150) students across the selected public secondary schools in the municipality of Roxas. Results: The research reveals Coordinated Functions of the Reproductive, Endocrine, and Nervous Systemas the most difficult science concept in Grade 10 Quarter III. Moreover, the research also presents a significant relationship between the performance of the students and the pedagogical content knowledge of their teacher, and that Teacher C utilizes the most preferable Pedagogical Content knowledge in teaching the assessed most difficult science concept. Conclusions: The Educational sector should consider the pedagogical content knowledge among teachers in reforming, making and developing a curriculum which would cater the arising difficulties in sciences. Results could also be used as a basis on developing programs and seminars to boost and improve the teaching styles and strategies of teachers in teaching sciences.