CPU cache has been used to bridge the processor-memory performance gap to enable high-performance computing. As the cache is of limited capacity, for its maximum efficacy it should (1) avoid caching data that are less likely to be accessed and (2) identify and cache data that would otherwise cost a program multiple memory accesses to reach. Unfortunately, existing cache architectures are inadequate on these two efforts. First, to cost-effectively exploit the spatial locality, they adopt a relatively large and fixed-size cache line as the caching unit. Thus, much of the space in a cache line can be wasted when the data locality is weak. Second, for easy use, the cache is designed to be transparent to programs, which hinders programs from fully exploiting its performance potentials. To address these problems, we propose a high-performance Software Defined Cache (SDC) architecture providing a simple and generic key-value abstraction that allows (1) caching data at a granularity smaller than a cache line, and (2) enabling programs to explicitly insert, retrieve, and invalidate data in the cache with new instructions. By providing a program with the ability of explicitly using the cache as a lookaside key-value buffer, SDC enables a much more efficient cache without disruptively changing the existing cache organization and without substantially increasing hardware cost. We have prototyped SDC on the gem5 simulator and evaluated it with various data index structures and workloads. Experiment results show that SDC can improve the cache performance for the workloads by up to 5.3× over current cache design.