I learned a lot about mold-making and casting in college at The Art Institute of Pittsburgh and with work experience. There are a few things I try to keep in mind while designing my parts for the greatest chance of success, and if I intend to have molds I can reuse several times.
Avoid creating undercuts in the part design. The more egregious the undercut, the more of a pain removing a cast from the mold will be. Depending on the durometer, or hardness of materials used, undercuts can make de-molding, the process of removing a cast part from a mold, very damaging for the mold and the part or even impossible to de-mold. Consider the parting lines of the mold when designing a part. How many mold pieces are you willing to have for the mold to mitigate undercuts?
Speaking of parting lines - the places where multiple mold pieces meet; if possible, try to put them alongside areas that can be well hidden. Typically parting lines create flashing or a seam of excess material on the cast part. This seam will need to be doctored in post-processing by removing excess material so that the seam is flush with the rest of the part. Strategically place the seam where it can most easily be made indistinguishable. If the seam can't be hidden, try to put it along easily accessible areas.
Consider the type of mold design the part can be cast in. A block mold? A matrix mold? Some other mold types? If the part is going to be cast in a block mold, avoid having deep vertical draws in the mold and parts. Deep draws make de-molding very difficult because they make such a strong vacuum between the casted part and the mold. Put draft angles on deep vertical walls instead. Make those draft angles at least 5°. The greater the draft angle, the easier it will be to de-mold, so it doesn't hurt to make draft angles as extreme as you can without sacrificing functionality and aesthetics. If deep draws are unavoidable, choose a different type of mold construction, such as a matrix mold. Matrix molds are more complicated to make but they can offer more flexibility and can save material costs. A silicone skin of about 0.5 inches or 12 mm surrounds the part cavity. That silicone skin is backed by a rigid material that can be removed easily from the silicone.