Venus and Mars likely had liquid water bodies on their surface early in the Solar System history. The surfaces of Venus and Mars are presently not a suitable habitat for life, but reservoirs of liquid water remain in the atmosphere of Venus and the subsurface of Mars, and with it also the possibility of microbial life. Microbial organisms may have adapted to live in these ecological niches by the evolutionary force of directional selection. Missions to our neighboring planets should therefore be planned to explore these potentially life-containing refuges and return samples for analysis. Sample return missions should also include ice samples from Mercury and the Moon, which may contain information about the biogenic material that catalyzed the early evolution of life on Earth (or elsewhere). To obtain such information, science-driven exploration is necessary through varying degrees of mission operation autonomy. A hierarchical mission design is envisioned that includes spaceborne (orbital), atmosphere (airborne), surface (mobile such as rover and stationary such as lander or sensor), and subsurface (e.g., ground-penetrating radar, drilling, etc.) agents working in concert to allow for sufficient mission safety and redundancy, to perform extensive and challenging reconnaissance, and to lead to a thorough search for evidence of life and habitability.