Ballastless track slabs are subjected to complex restraint conditions and operational environments, making deformation-induced cracking a critical factor affecting durability and service performance. Conventional cracking resistance evaluations generally rely on individual parameters, which cannot adequately describe the relationship between cracking driving forces and resistance capacity under restrained conditions. This study proposes a cracking resistance evaluation and mixture optimization framework for ballastless track slabs. A cracking resistance index (CRI) was developed based on the competition between deformation-induced stress demand and flexural cracking resistance by integrating shrinkage deformation, elastic modulus, and flexural strength. The proposed CRI is intended as a comparative index for quantitatively assessing the relative cracking resistance among different concrete mixtures. The effects of key mixture parameters, including water-to-binder ratio, sand ratio, binder content, air-entraining agent dosage, and internal curing admixture dosage, on fresh properties, mechanical performance, shrinkage behavior, and CRI were systematically investigated. The results indicated that the water-to-binder ratio, air-entraining agent dosage, and internal curing admixture dosage were the dominant factors affecting CRI. In particular, internal curing reduced shrinkage deformation and consequently decreased the CRI, which may be attributed to improved internal moisture conditions. Based on the Box–Behnken design method, a response surface model (RSM) was established to optimize mixture proportions with the objective of minimizing CRI while satisfying the mechanical requirements for C40 ballastless track slab concrete. A preliminary experimental verification using three replicate specimens prepared with the optimized mixture showed good consistency between the RSM-predicted and measured CRI values, with a relative error of 3.81%. The proposed framework provides a quantitative approach for cracking resistance-oriented mixture optimization of concrete used in ballastless track slab.