This study examined socio-economic factors contributing to neonatal mortality in Rungwe District, Mbeya Region. The study sample consisted of 50 respondents from Kibanja and Mpumbuli villages and Kissa Government Health Centre with different informants. Data were collected through questionnaire interviews and were analysed using MS-Excel and comparisons of significant variable means using Least Significance Difference (LSD) at 5% probability following two-sided t-test against zero. GenStat software was used to check for correlations among response variables but they were all insignificant (P>0.05). The findings indicated that the mean socio-economic factors (63.9%, 75%, 53.6%) and stakeholders’ contribution to reduction of neonatal mortality (54.4%, 55.5%, 47.1%) each factor and its corresponding magnitude in the order of Kibanja, Mpumbuli and Kissa Health Centre, respectively, were significant (P<0.05). However, results indicated that in Kibanja village the mean care taken by mothers soon after delivery (33.3%), delivery practices (33.3%) and negative impact of neonatal mortality (37%) were statistically at pair (P>0.05). In Mpumbuli village the mean socio-economic factors (75%), delivery practices (38.9%), stakeholders’ contribution to reduction of neonatal mortality (55.5%) and the perceived negative impact of neonatal mortality (59.2%) were statically significant (P<0.05) from care taken by mothers soon after delivery. Furthermore, at Kissa Health Centre the mean socio-economic factors (53.6%), and stakeholders’ contribution to reduction of natal mortality (47.1%) were statically significant (P<0.05) from other studied factors. Results indicated that care taken by mothers soon after delivery (28.5%), delivery practices (23.8%) and the perceived negative impact of neonatal mortality (28.6%) did not differ significantly (P>0.05). Based on the findings of this study, it is recommended that further study be conducted on the same study focusing on sectors influencing neonatal mortality in the area other than socio-economic factors.