Microplastics (MPs) are increasingly being studied because they have become ubiquitous in aquatic and terrestrial environments. However, little is known about the negative effects of co-contamination by polypropylene microplastic (PP MPs) and heavy metal mixtures on terrestrial environment and biota. This study assessed the adverse effects of co-exposure to PP MPs and heavy metal mixture (Cu2+, Cr6+, and Zn2+) on soil quality and the earthworm Eisenia fetida. Soil samples were collected in the Dong Cao catchment, near Hanoi, Vietnam, and analyzed for changes in extracellular enzyme activity and carbon, nitrogen, and phosphorus availability in the soil. We determined the survival rate of earthworms Eisenia fetida that had ingested MPs and two doses of heavy metals (the environmental level — 1 × — and its double — 2 ×). Earthworm ingestion rates were not significantly impacted by the exposure conditions, but the mortality rate for the 2 × exposure conditions was 100%. Metal-associated PP MPs stimulated the activities of β-glucosidase, β-N-acetyl glucosaminidase, and phosphatase enzymes in soil. Principle component analysis showed that these enzymes were positively correlated with Cu2+ and Cr6+ concentrations, but negatively correlated with microbial activity. Zn2+ showed no correlation with soil extracellular enzyme activity or soil microbial activity. Our results showed that co-exposure of earthworms to MPs and heavy metals had no impact on soil nitrogen and phosphorus but caused a decrease in total soil carbon content, with a possible associated risk of increased CO2 emissions.