Dairy cattle genetic improvement has been practiced so far in Ethiopia to improve the productive and reproductive performance of dairy cows. However, the achievement has been limited due to poor husbandry practice, shortage of feed, inappropriate breeding scheme, inefficient AI service, and mismatch between management and genetic intervention under smallholder farmers conditions. This study was aimed to investigate the synergetic effect of genetic and non-genetic factors on reproductive and milk production performance of crossbred dairy cows under smallholder dairy farmer’s condition in selected milk shed areas of Ethiopia. A total of 72 smallholder dairy farmers who had at least two crossbred dairy cows and recruited, and non-recruited by different projects were purposively selected from three administrative regions of Ethiopia (Amhara, Oromia and South Nation, Nationalities, and Peoples). During the intervention period, this study had two phases. In first phase, the selected smallholder dairy farmers were assigned in to three treatment groups (T 1 (control), T 2 (previously trained by the projects) and T 3 (received additional enhanced training and improved feed input). In second phase, treatment groups that were regarded as control (T 1 ) during the first phase had received enhanced training and improved feed input following the same protocols with previous one. On the other hand, treatment groups that were received enhanced training and improved feed input (T 3 ) considered as control treatment group for the second phase intervention study. Tail hair samples for genetic profiling of breed composition were collected from all experimental cows in the study. According to their Holstein Frisian blood level, crossbred cows were classified into four genetic groups (<25%, 25-50%, 51-75% and >75%). In addition, experimental cows were also grouped based on their parity. Performance data collection was collected over for the period of three years starting from 2020 to 2022. A general linear model procedure of the statistical analysis system (SAS version, 9.0) was used to analyse the reproductive and productive performance data. The analysis of variance showed that statistically non-significant(P>0.05) difference was observed for the effect of genotype by treatment and genotype by parity interactions on age at first service (AFS), age at first calving (AFC), calving interval (CI), days open and number of services per conception (NSPC) traits and some milk production traits such as lactation length (LL) and first lactation length (FLL). The results of fixed effect analysis revealed that the influence of genotype had a significant effect in age at first service (P<0.0001), age at first calving (<0.0001), calving interval (<0.01) and number of services per conception (<0.001) traits. However, a statistically nonsignificant (p>0.05) difference was observed for the main effect of treatments on age at first service (AFS), age at first calving (AFC), calving interval (CI), and number of services per conception (NSPC) traits. The study also revealed that calving interval (p<0.01) and days open (p<0.05) traits were significantly influenced by the interaction effect of treatment and parity interaction. The analysis of variance showed that the interaction effect of genotypes by treatments and genotype by parity caused significant (p<0.0001) in lactation milk yield and daily milk yield traits. In addition, first lactation milk yield (p<0.001) and first lactation daily milk yield (p<0.01) traits were significantly influenced by the interaction effect of genotypes and treatments. Lactation length was significantly influenced by the main effect of genotype (p<0.0001) and treatment (p<0.001). A statistically significant effect of genotypes (p≤ 0.01) and treatments (p≤0.001) were observed on first lactation milking days trait. The overall least square mean value of first lactation milk yield, first lactation daily milk yield and first lactation length for the interaction effect of genotype and treatments were 2297.0 ±53.42 liters, 7.3 ± 0.15 liters and 309.0±2.00 days, respectively. The overall least square mean value of daily milk yield, lactation length and lactation milk yield for the interaction effect of genotype by treatment and genotype by parity were 8.0±0.16 liters, 298.2±2.51 days and 2419.8 ± 61.56 liters, respectively. In conclusion, the combined effect of genetic and non-genetic intervention under smallholder farmers condition resulted in increased milk production performance of primiparous and multiparous crossbred dairy cows. However, no significant difference was observed in reproductive performance of crossbred for synergetic effect of those factors.