Apart from creating a custom Mii-like character, players may also modify their houses and build furniture and appliances using a selection of building blocks. This gives the player more building options, allowing them to create objects by using blueprints, a change from the usual virtual catalog found in The Sims. There are 80 characters with whom the player may interact in the Wii version (30 characters in the Nintendo DS version), such as a mad scientist, a magician, a librarian and a chef. Some of these characters may ask the player to build things for them. As with previous Sims games, meeting people and forming relationships is a major gameplay focus. Becoming a Sim's best friend will earn the player either a special blueprint not available anywhere else in the game, or a style of clothing for their wardrobe. Players can also earn blueprints by preforming tasks for Commercial Sims (Sims who have their own businesses). Typically this involves building around 5-10 items for Sims, depending the Star Level (the 1-5 level) of the player's town and the essences they have access to.
A feature new to MySims is Essences. They can be found in various locations in town or by interacting with Sims or objects. Essences are used for a number of things including paint for the walls of houses, construction of items, as well as decoration.
Unlike previous Sims titles, Sims in this game do not have needs or wants.
Compared to previous Sims titles, MySims has a more anime-inspired look, with Chibi character designs. This was Emmy Toyonaga's idea; in Official Nintendo Magazine she remarked: "Well, Mario and other Nintendo characters are pretty short and stubby. Also, being Japanese, I'm used to the mindset that fun games should have shorter, stubbier characters. So these characters kind of came naturally".In Nintendo Power, designer Robin Hunicke said that the character designs also imply youthfulness, and that the aesthetic was chosen for world-wide appeal, while referring to the lesser sales of previous Sims games in Japan compared to other territories.
According to the Official Nintendo Magazine one of the characters, Chaz, is based on their editor, Chandra Nair.