This study examined the relationship between personal and work-related factors and job satisfaction of teachers of pupils with special needs in special schools on the mainland in Lagos State, Nigeria. Ninety-three teachers from 8 special/inclusive schools participated in the study. Two research hypotheses were formulated for the study. The study employed the descriptive survey research design, while a structured research instrument “Teachers job Satisfaction Scale” (α = .78) was used for data collection. The data generated were analysed using descriptive statistics and inferential statistics of Pearson Product Moment Correlation and hierarchical multiple regression at 0.05 level of significance. Job satisfaction of teachers of pupils with special needs significantly correlated with gender (r = -.415), workload (r = .342), work environment (r = .286), and organizational support (r = .526). Furthermore, gender –F (1, 91) = 18.899) –and organizational support –F (1, 87) = 4.532) –were the highest predictors of job satisfaction of teachers of pupils with special needs. It is recommended that teachers of pupils with special needs should be motivated to play active roles in special schools. Also policies that will support development and retention of teachers in special schools is encouraged.