This study investigated the effect of Content-Focused Coaching (CFC) on academic performance and retention in difficult biology topics among Senior Secondary School students in Zamfara State, Nigeria. Quasi-experimental design was adopted for the study. Multi-stage sampling technique was employed to select 1005 students (480 males, 525 females) and 48 teachers from 166 public schools. The Biology Performance Test, with a reliability coefficient of 0.77, was used for data collection. Teacher participants were exposed to CFC for seven weeks, focusing on six identified perceived difficult biology topics. Data collected were analysed using ANCOVA at a 0.05 significance level. Results showed significant differences in performance (F(3, 966)=111.394, p<0.05) and retention (F(3, 966)=164.035, p<0.05) among students taught by teachers with Pedagogical Content Knowledge and those taught by Biological Content Knowledge-only who were exposed to CFC. Gender differences were observed, with CFC being effective for both genders. Whereas, students taught by teachers with Pedagogical Knowledge-only exposed to CFC did not significantly improved in performance and retention, and showed notable gender differences similar to those taught by teachers in the control group. The study recommended CFC for professional development of biology teachers.