The benefit sof municipal solid waste (MSW) compost on soil health and plant productivity are well known, but not its long-term effect on soil microbial and plant metabolic pathways. A 5-year study with annual (AN), biennial (BI) and no (C, control) MSW compost application were carried out to determine the effect on soil properties, microbiome function, and plantgrowth and TCA cycle metabolites profile of green beans (Phaseolus vulgaris), lettuce (Latuca sativa) and beets (Beta vulgaris). MSW compost increased soil nutrients and organic matter leading to a significant (p < 0.05) increase in AN-soil water-holding capacity followed by BI-soil compared to C-soil. Estimated nitrogen release in the AN-soil was ca. 23% and 146% more than in BI-soil and C-soil, respectively. Approximately 44% of bacterial community due to compost. Deltaproteobacteria, Bacteroidetes Bacteroidia, and Chloroflexi Anaerolineae were overrepresented in compost amended soils compared to C-soil. A strong positive association existed between AN-soil and 18 microbial metabolic pathways out of 205. Crop yield in AN-soil were increased by 6–20% compared to the BI-soil, and by 35–717% compared to the C-soil. Plant tricarboxylic acid cycle metabolites were highly (p < 0.001) influenced by compost. Overall, microbiome function and TCA cycle metabolites and crop yield were increased in the AN-soil followed by the BI-soil and markedly less in C-soil. Therefore, MSW compost is a possible solution to increase soil health and plants production in the medium to long term. Future study must investigate rhizosphere metabolic activities.