Biology as a discipline is a pre-requisite field of study at O-level for very many professional careers in the realm of Medicine, Agriculture, Forestry, Teaching, Sociology among others. This means that is a critical subject that requires proper teaching and learning at secondary school or O-level it is a concern to note that in Kenya from 2016 to date the in biology is wanting. The following data attest to this. The performance in Biology at Kenya Certificate of Secondary Education (KCSE) level is very low nationally and even at Sub County level despite provision of educational resources or inputs by the government. Thus, in the whole country candidates who sat KCSE examinations in the year 2016 only 71,348(13.99%) out of 509,822 scored C+ and above, in 2017, only 11,503(2.1%) candidates out of 546,014 scored C+ and above and in 2018, only 33,126(5.66%) candidates out of 584,924 scored C+ and above. In Ndhiwa Sub County, the performance of Biology was been far much below the average for the last four years registering mean scores of: 4.83 in 2015, 2.90 in 2016, 2.27 in 2017 and 2.90 in 2018. The objective of this study was therefore to determine influence of school factors on students’ performance in Biology in Ndhiwa Sub-County. The study established that school factors accounted for 7% of the variation in students’ performance in Biology but the influence was not statistically significant at the p-value of 0.05. This means that there is serious wastage in utilization of educational resources such as finance, library, Biology laboratory, revision materials in Biology and use of ICT in teaching and learning provided by the government and parents. This is signified by the negative relationship between most school factors and students performance as revealed by multiple regression analysis. The study recommended that Quality Assurance and Standards Officers and principals of secondary schools should ensure optimal use of educational resources to remedy the situation. The findings of this study will inform policy formulation and decision making with a view to enhancing student performance in Biology.