One of the most important challenges facing current and future generations is how climate change and continuous population growth adversely affect food security. To address this, the food system needs a complete transformation where more is produced in non-optimal and space-limited areas while reducing negative environmental impacts. Fruits and vegetables, essential for human health, are high-value-added crops, which are grown in both greenhouses and open field environments. Here, we review potential practices to reduce the impact of climate variation and ecosystem damages on fruit and vegetable crop yield, as well as highlight current bottlenecks for indoor and outdoor agrosystems. To obtain sustainability, high-tech greenhouses are increasingly important and biotechnological means are becoming instrumental in designing the crops of tomorrow. We discuss key traits that need to be studied to improve agrosystem sustainability and fruit yield.