The work aims to study the cold chain path optimization problem based on the remaining shelf life loss cost of aquatic products, so as to reduce the shelf life loss of aquatic products due to untimely delivery during transportation. The shelf life loss cost method was introduced and a cold chain transportation path optimization model (VRP-SI model) was established based on the remaining shelf life of aquatic products. The shelf life loss cost was studied in segments according to different delivery times of the cold chain vehicles. The optimization objective was to minimize the total delivery cost. The model was solved by combining an improved genetic algorithm and a simulated annealing algorithm, and further simulation experiments were conducted with Solomon examples. The results showed that the VRP-SI model reduced expenditures by 14.28%, 12.86%, and 15.58% respectively compared with the ordinary path optimization model, and reduced the overall cost by 8.41%, 6.07%, and 5.25% respectively. In conclusion, the VRP-SI model can reduce the total delivery cost and provide an effective solution for the cold chain path optimization problem of aquatic products.