Heavily focusing on its characters, SAMURAI WARRIORS: Spirit of Sanada follows Masayuki Sanada, the clan's patriarch, from his very first battle and continues through following his second son Yukimura, from his birth in 1567. Yukimura was a pure natured yet reckless child who grew up with his elder siblings watching out for him and strived throughout his life to give his best for the clan. Both he and his brother, Nobuyuki, were determined to be as wise as their father and the pair diligently trained together to follow in his footsteps.

Witness life in a Castle Town as it grows from quiet and peaceful to bustling and prosperous. Reside during missions and prepare for the next battle or talk to the officers and townspeople to gain a deeper insight into their daily lives. The fear of war and the celebration of victory both have their own effect on the morale of the people, and some will ask for help with their troubles by offering missions.

Over the course of the story, the Castle Town expands, granting a greater array of facilities for players to utilise. The Blacksmith uses materials to improve and upgrade weapons to grant an upper-hand in combat, Stables allow for horses to be purchased and prepared for the next mission, Shops sell rare and unique items which will replenish an officer's health and musou gauges, and the Dojo provides a training ground where one can learn new skills or enhance older ones. A Teahouse is also present, here officers can talk with one another and exchange gifts. Finding the correct gift will result in raised favour with another officer which allows them to join forces on the front line.

Gather material through compelling Mini Games and use them across the town's facilities. Planting seeds and harvesting ingredients in the Hoeing mini-game produces rare goods which cannot be found on the battlefield, Fishing allows officers to approach a body of water to catch a wide variety of different fish breeds to use as gifts, and the Jinzō offers an entertaining version of the Shell game.