The study investigated challenges affecting the teaching and learning of Integrated Science in rural Junior High Schools (JHSs) in the Effutu Municipality in the central region of Ghana. A qualitative approach was employed. Purposive sampling was employed to select six rural JHSs from the municipality. A closed-structured interview was used to collect data from head teachers, teachers, and pupils, and then analyzed. The study revealed that inadequate instructional materials and poor proficiency of pupils in the English language affected the teaching and learning of Integrated Science. The study concluded that if these challenges were addressed, teaching and learning of Integrated Science would be improved in rural JHSs. It is recommended that Integrated Science teachers should be trained to improvise instructional material using materials in the environment to teach the subject. This would help pupils to conceptualize scientific concepts as they interact with the materials. Again, pupils should be encouraged to build their English vocabulary to express and make informed contributions to the teaching and learning of integrated science.